WO2015125819A1 - Fine particle production method - Google Patents

Fine particle production method Download PDF

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Publication number
WO2015125819A1
WO2015125819A1 PCT/JP2015/054427 JP2015054427W WO2015125819A1 WO 2015125819 A1 WO2015125819 A1 WO 2015125819A1 JP 2015054427 W JP2015054427 W JP 2015054427W WO 2015125819 A1 WO2015125819 A1 WO 2015125819A1
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WO
WIPO (PCT)
Prior art keywords
fine particles
fluid
raw material
fine particle
stirring
Prior art date
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PCT/JP2015/054427
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French (fr)
Japanese (ja)
Inventor
榎村眞一
Original Assignee
エム・テクニック株式会社
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Filing date
Publication date
Application filed by エム・テクニック株式会社 filed Critical エム・テクニック株式会社
Priority to EP15752000.8A priority Critical patent/EP3112017A4/en
Priority to JP2016504131A priority patent/JPWO2015125819A1/en
Priority to CN201580009158.8A priority patent/CN106029216B/en
Priority to US15/119,965 priority patent/US20170246595A1/en
Priority to KR1020167021490A priority patent/KR20160122716A/en
Publication of WO2015125819A1 publication Critical patent/WO2015125819A1/en

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/0053—Details of the reactor
    • B01J19/0066—Stirrers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/404—Indoles, e.g. pindolol
    • A61K31/405—Indole-alkanecarboxylic acids; Derivatives thereof, e.g. tryptophan, indomethacin
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F21/00—Dissolving
    • B01F21/10—Dissolving using driven stirrers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
    • A61K8/4913—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid
    • A61K8/492—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid having condensed rings, e.g. indol
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
    • B01F23/40—Mixing liquids with liquids; Emulsifying
    • B01F23/41—Emulsifying
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01F27/27—Mixers with stator-rotor systems, e.g. with intermeshing teeth or cylinders or having orifices
    • B01F27/271—Mixers with stator-rotor systems, e.g. with intermeshing teeth or cylinders or having orifices with means for moving the materials to be mixed radially between the surfaces of the rotor and the stator
    • B01F27/2712—Mixers with stator-rotor systems, e.g. with intermeshing teeth or cylinders or having orifices with means for moving the materials to be mixed radially between the surfaces of the rotor and the stator provided with ribs, ridges or grooves on one surface
    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B01F27/80—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis
    • B01F27/81—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis the stirrers having central axial inflow and substantially radial outflow
    • B01F27/812—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis the stirrers having central axial inflow and substantially radial outflow the stirrers co-operating with surrounding stators, or with intermeshing stators, e.g. comprising slits, orifices or screens
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    • B01F27/80—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis
    • B01F27/84—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis with two or more stirrers rotating at different speeds or in opposite directions about the same axis
    • B—PERFORMING OPERATIONS; TRANSPORTING
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    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
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    • B01F27/80—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis
    • B01F27/86—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis co-operating with deflectors or baffles fixed to the receptacle
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    • B01F27/00—Mixers with rotary stirring devices in fixed receptacles; Kneaders
    • B01F27/80—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis
    • B01F27/90—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis with paddles or arms 
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01F27/00—Mixers with rotary stirring devices in fixed receptacles; Kneaders
    • B01F27/80—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis
    • B01F27/92—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis with helices or screws
    • B01F27/921—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis with helices or screws with helices centrally mounted in the receptacle
    • B01F27/9214—Mixers with rotary stirring devices in fixed receptacles; Kneaders with stirrers rotating about a substantially vertical axis with helices or screws with helices centrally mounted in the receptacle with additional mixing elements other than helices; having inner and outer helices; with helices surrounding a guiding tube
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/20—Measuring; Control or regulation
    • B01F35/21—Measuring
    • B01F35/211—Measuring of the operational parameters
    • B01F35/2115—Temperature
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F35/00—Accessories for mixers; Auxiliary operations or auxiliary devices; Parts or details of general application
    • B01F35/20—Measuring; Control or regulation
    • B01F35/22—Control or regulation
    • B01F35/221—Control or regulation of operational parameters, e.g. level of material in the mixer, temperature or pressure
    • B01F35/2214—Speed during the operation
    • B01F35/22142—Speed of the mixing device during the operation
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/18—Stationary reactors having moving elements inside
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/18—Stationary reactors having moving elements inside
    • B01J19/1887—Stationary reactors having moving elements inside forming a thin film
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J4/00—Feed or outlet devices; Feed or outlet control devices
    • B01J4/001—Feed or outlet devices as such, e.g. feeding tubes
    • B01J4/002—Nozzle-type elements
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B48/00—Quinacridones
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B67/00—Influencing the physical, e.g. the dyeing or printing properties of dyestuffs without chemical reactions, e.g. by treating with solvents grinding or grinding assistants, coating of pigments or dyes; Process features in the making of dyestuff preparations; Dyestuff preparations of a special physical nature, e.g. tablets, films
    • C09B67/0033—Blends of pigments; Mixtured crystals; Solid solutions
    • C09B67/0034—Mixtures of two or more pigments or dyes of the same type
    • C09B67/0036—Mixtures of quinacridones
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B67/00—Influencing the physical, e.g. the dyeing or printing properties of dyestuffs without chemical reactions, e.g. by treating with solvents grinding or grinding assistants, coating of pigments or dyes; Process features in the making of dyestuff preparations; Dyestuff preparations of a special physical nature, e.g. tablets, films
    • C09B67/0071—Process features in the making of dyestuff preparations; Dehydrating agents; Dispersing agents; Dustfree compositions
    • C09B67/0084—Dispersions of dyes
    • C09B67/0085—Non common dispersing agents
    • C09B67/009—Non common dispersing agents polymeric dispersing agent
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B67/00—Influencing the physical, e.g. the dyeing or printing properties of dyestuffs without chemical reactions, e.g. by treating with solvents grinding or grinding assistants, coating of pigments or dyes; Process features in the making of dyestuff preparations; Dyestuff preparations of a special physical nature, e.g. tablets, films
    • C09B67/0071—Process features in the making of dyestuff preparations; Dehydrating agents; Dispersing agents; Dustfree compositions
    • C09B67/0092—Dyes in solid form
    • C09B67/0095—Process features in the making of granulates
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09B—ORGANIC DYES OR CLOSELY-RELATED COMPOUNDS FOR PRODUCING DYES, e.g. PIGMENTS; MORDANTS; LAKES
    • C09B67/00—Influencing the physical, e.g. the dyeing or printing properties of dyestuffs without chemical reactions, e.g. by treating with solvents grinding or grinding assistants, coating of pigments or dyes; Process features in the making of dyestuff preparations; Dyestuff preparations of a special physical nature, e.g. tablets, films
    • C09B67/0097—Dye preparations of special physical nature; Tablets, films, extrusion, microcapsules, sheets, pads, bags with dyes
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
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    • B01F21/50—Elements used for separating or keeping undissolved material in the mixer
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01F2101/00—Mixing characterised by the nature of the mixed materials or by the application field
    • B01F2101/30—Mixing paints or paint ingredients, e.g. pigments, dyes, colours, lacquers or enamel
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
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    • B01J2219/0077—Baffles attached to the reactor wall inclined
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Definitions

  • the present invention relates to a method for producing fine particles.
  • Metals, oxides, biological ingestions such as pharmaceuticals, foods and cosmetics, and fine particles such as pigments are required in a wide range of industries.
  • the method for producing fine particles is generally performed by using a flask, beaker, tank, or the like as described in Patent Document 1 for reactions such as an anti-solvent method, crystallization, oxidation, and reduction.
  • a container When such a container is used, it is difficult to keep the concentration and temperature uniform in the container, so that the particle size distribution of the resulting fine particles tends to be widened, and alloys and composite oxidations containing two or more elements
  • a method for producing fine particles using a microreactor as described in Patent Document 2 is also provided.
  • a microreactor when a general microreactor is used, clogging of reactants and scale-up cannot be performed. There are many current issues. Therefore, a method for producing homogeneous and uniform fine particles stably, with low energy and resource saving has been appealed.
  • Patent Document 3 Even when the method described in Patent Document 3 is used, when it is difficult to stably produce fine particles, or when producing fine particles containing two or more kinds of molecules and elements, There are variations in local element ratios, and it may be difficult to produce uniform and uniform fine particles.
  • the operating conditions of the apparatus such as the prescription of the fluid to be processed, the liquid feeding amount, the temperature, and the rotational speed of the processing surface are simply changed. Therefore, it is difficult to achieve a desired crystallinity, crystal type or specific crystal type composition ratio of the generated fine particles, and properties / characteristics of the fine particles such as crystallinity, crystal type or specific crystal type composition ratio.
  • No specific method for freely controlling the image is disclosed, leaving room for improvement.
  • the “constituent ratio of a specific crystal type” refers to a ratio of a crystal component of a specific crystal type to a plurality of crystal components of the crystal type when the generated fine particles have a plurality of crystal types. .
  • the present invention has been made in view of the above situation, and provides a production method capable of obtaining desired fine particles with respect to properties / characteristics such as crystallinity, crystal type, or composition ratio of a specific crystal type. With the goal.
  • the method for producing fine particles of the present invention comprises a dissolving step of dissolving at least one kind of fine particle raw material in a solvent using a stirrer having a rotating stirring blade, and obtaining the fine particle raw material solution from the fine particle raw material solution.
  • At least two types of deposition solvents for depositing and the fine particle raw material solution disposed opposite to each other and capable of approaching / separating at least one rotating relative to the other.
  • the gist is to control the crystallinity of the fine particles obtained in the precipitation step by increasing or decreasing the stirring energy.
  • the gist is to control the crystal form of the fine particles obtained in the precipitation step by increasing or decreasing the stirring energy.
  • at least one of the above conditions is changed in the stirring energy defined by the stirring time condition by the stirrer, the peripheral speed condition of the stirring blade, and the temperature condition of the fine particle raw material solution.
  • the power P (work per unit time) of the stirrer is obtained by the following formula (1).
  • Stirring power P [kw] Np ⁇ ⁇ ⁇ n 3 ⁇ d 5 (1)
  • the precipitation method of the fine particles in the precipitation step is not particularly limited, but typical examples include an acid pasting method, an alkali paste method, and a poor solvent method. Then, prior to the precipitation step by the precipitation method represented by the precipitation method exemplified above, the ratio of the crystallinity of the fine particles to the particle diameter of the fine particles is increased by increasing the stirring energy in the dissolution step. It can implement as what controls. Further, the present invention deposits the fine particles by a precipitation step by various precipitation methods typified by the precipitation method exemplified above, and the fine particles have a plurality of crystal types, and a plurality of crystal type crystals.
  • the ratio of the crystal component of the specific crystal type to the component is the specific crystal type constituent ratio, and the constituent ratio of the specific crystal type to the particle diameter of the fine particles is increased by increasing the stirring energy in the dissolving step. It can implement as what controls so that the ratio of may rise.
  • the present invention can be carried out with the fine particles being pigment fine particles.
  • Pigment fine particles are used in a wide variety of fields such as paints, printing inks, toners, inkjet inks, color filters, etc., but in particular, as one of the fields where highly functional materials are required in practice,
  • the color filter pigments for LCDs are required to have high transmittance characteristics, and there are “crystallinity” and “constituent ratio of specific crystal type” as indices relating to the transmittance characteristics. By controlling these indicators, it is possible to obtain pigment fine particles with high transmittance.
  • the crystal type of 2,9-dimethylquinacridone (CI Pigment Red 122) (hereinafter referred to as PR122) includes an ⁇ -type crystal and a ⁇ -type crystal, and both are usually mixed.
  • ⁇ -type crystals are stable, and ⁇ -type crystals are metastable. The higher the proportion occupied by ⁇ -type crystals, the more yellow the yolk is, and it is necessary to create crystal proportions according to the target color tone.
  • the proportion of the ⁇ -type crystal or ⁇ -type crystal in the crystal component of the ⁇ -type crystal and the ⁇ -type crystal in PR122 is referred to as “constituent ratio of the specific crystal type”.
  • the ratio of the ⁇ -type crystal to the total crystal component of the crystal and the ⁇ -type crystal is called “ ⁇ -type crystal ratio”.
  • a crystal component and an amorphous component are mixed, and the ratio of the crystallized component to the total of the crystallized component and the amorphous component is referred to as “crystallinity”.
  • crystallinity the higher the crystallinity, the better the durability against light, heat, moisture, etc., which is well known.
  • the degree of crystallinity of the fine particles obtained in the precipitation step is controlled by increasing or decreasing the stirring energy in the dissolution step
  • the specific crystal type composition ratio of the fine particles obtained in the precipitation step is controlled by increasing or decreasing the stirring energy in the dissolving step.
  • the PR122 fine particles used as the ink-jet ink have a high “crystallinity”, and it is necessary to make “ ⁇ -type crystal ratio” and “ ⁇ -type crystal ratio” separately according to the target color tone.
  • the present invention can be carried out as the fine particles are other than pigment fine particles.
  • indomethacin which is a pharmaceutical
  • the crystallinity of the fine particles obtained in the precipitation step by increasing or decreasing the stirring energy in the dissolution step.
  • Indomethacin has a plurality of crystal types, and representative examples include a stable ⁇ -type crystal, an unstable ⁇ -type crystal, and a metastable ⁇ -type crystal. Usually, these crystal forms coexist, but the higher the proportion of ⁇ -type crystals, the more stable characteristics.
  • the proportion of the ⁇ -type crystal, ⁇ -type crystal, or ⁇ -type crystal in the crystal component of ⁇ -type crystal, ⁇ -type crystal, and ⁇ -type crystal in indomethacin is referred to as the “constituent ratio of the specific crystal type”.
  • the proportion of ⁇ -type crystals in the crystal component of ⁇ -type crystals, ⁇ -type crystals, and ⁇ -type crystals in indomethacin is called “ ⁇ -type crystal ratio”.
  • the degree of crystallinity of fine particles obtained in the precipitation step is controlled by increasing or decreasing the stirring energy in the dissolving step, and stirring in the dissolving step. Since the crystal form of the fine particles obtained in the precipitation step can be controlled by increasing or decreasing the energy, it is considered that the same tendency is exhibited even in other substances.
  • the present invention controls the so-called dissolved state by increasing or decreasing the stirring energy, which is physical energy, in the dissolving step, in other words, changing the dissolved state of the fine particle raw material solution or changing the cluster forming state.
  • the present invention provides one of the peripheral speed condition, the stirring time condition, and the temperature condition in the dissolving step when producing fine particles having a particle diameter, a crystallinity, and a crystal type set to specific conditions.
  • first condition condition
  • second third condition condition
  • the first condition that satisfies the specific condition is determined.
  • the particle size, crystallinity, and crystal type of the fine particles in the precipitation step are changed.
  • Manufacturing at least one of the second and third conditions for the remaining two different from at least one to produce fine particles satisfying the specific conditions in terms of particle diameter, crystallinity and crystal type can be implemented.
  • the microparticles in the precipitation step By determining the peripheral speed condition that satisfies the specific condition for the particle diameter, and maintaining the determined peripheral speed condition, by changing at least one of the stirring time condition and the temperature condition, By determining the stirring time condition and the temperature condition satisfying the specific conditions for the crystallinity and crystal form of the fine particles in the precipitation step, the particle diameter, the crystallinity, and the crystal form satisfy the specific conditions. It can be carried out as a method for producing fine particles.
  • At least two kinds of fluids to be treated are used, and at least one kind of fluid to be treated is the fine particle raw material solution, and the fine particle raw materials are Among the fluids to be treated other than the solution, at least one kind of fluid to be treated is the precipitation solvent, and a fluid pressure imparting mechanism for imparting pressure to the fluid to be treated, and among the at least two processing surfaces A first processing part having a first processing surface, and a second processing part having a second processing surface of the at least two processing surfaces, the processing parts being relatively Each of the processing surfaces constitutes a part of a sealed flow path through which the fluid to be processed to which the pressure is applied flows. Of the processing part and the second processing part.
  • At least the second processing portion includes a pressure receiving surface, and at least a part of the pressure receiving surface is constituted by the second processing surface, and the pressure receiving surface is covered by the fluid pressure applying mechanism.
  • a force is generated to move the second processing surface away from the first processing surface, and at least one of the facing and disengagement disposed is opposed.
  • the fluid to be processed is passed between the first processing surface and the second processing surface that rotate relative to the other, so that the fluid to be processed is the thin film. It can be implemented as a method for producing fine particles in which a fluid is formed and fine particles are precipitated in the thin film fluid.
  • At least any one of the fluids to be processed passes between the processing surfaces while forming the thin film fluid
  • a separate introduction path independent of the flow path through which at least one of the fluids flows is provided, and at least one of the first processing surface and the second processing surface is in the introduction path.
  • At least one opening that communicates, and at least one fluid different from the at least one fluid is introduced between the processing surfaces from the opening, and the fluid to be treated is placed in the thin film It can be implemented as a method of producing fine particles that are mixed in a fluid and fine particles are precipitated in the thin film fluid.
  • the present invention makes it possible to control the crystallinity and crystal form of fine particles, and to continuously produce fine particles with controlled crystallinity and crystal form.
  • the fine particle raw material solution is prepared by using a stirrer having a rotating stirring blade, and at that time, three conditions (the stirring time, the peripheral speed of the stirring blade, and the fine particle raw material solution are defined.
  • the so-called dissolved state is controlled by simply changing the processing conditions of increasing or decreasing the stirring energy, in other words, changing the dissolved state of the fine particle raw material solution, Since it was possible to change the cluster formation state and to prepare a fine particle raw material solution that was dissolved or dispersed at the molecular level, the crystallinity and crystal form of the fine particles deposited in the subsequent precipitation step
  • the desired fine particles can be obtained with respect to properties / characteristics such as crystallinity and crystal form. Furthermore, it is possible to make fine particles according to the purpose.
  • FIG. 1 is a schematic cross-sectional view of a fluid processing apparatus according to an embodiment of the present invention.
  • A is a schematic plan view of a first processing surface of the fluid processing apparatus shown in FIG. 1, and
  • A) is sectional drawing of the 2nd introducing
  • B) is the principal part enlarged view of the processing surface for demonstrating the 2nd introducing
  • 4 is a graph showing changes in crystallinity / average particle diameter and ⁇ -type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation temperature of the second fluid in Examples 1 to 3.
  • 6 is a graph showing changes in crystallinity / average particle diameter and ⁇ -type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid in Examples 4 to 7.
  • 6 is a graph showing changes in crystallinity / average particle diameter and ⁇ -type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid in Examples 8 to 11.
  • 6 is a graph showing changes in the degree of crystallinity / average particle size and ⁇ -type crystal ratio / average particle size of PR122 fine particles with respect to the preparation time of the second fluid in Examples 12 to 16.
  • 6 is a graph showing changes in crystallinity / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid in Examples 8 to 11 and Examples 12, 13, 15, and 16.
  • 6 is a graph showing changes in ⁇ -type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid in Examples 8 to 11 and Examples 12, 13, 15, and 16.
  • 6 is a graph showing changes in crystallinity / average particle diameter of PR122 fine particles with respect to the peripheral speed at the time of preparing the second fluid in Examples 17-22.
  • 6 is a graph showing changes in ⁇ -type crystal ratio / average particle diameter of PR122 fine particles with respect to the peripheral speed at the time of preparing the second fluid in Examples 17-22.
  • 6 is a graph showing changes in the crystallinity / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid in Examples 23 to 31.
  • 6 is a graph showing changes in ⁇ -type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid in Examples 23 to 31.
  • FIG. 10 is a graph showing changes in crystallinity / average particle diameter of PR122 fine particles with respect to the preparation temperature of the second fluid in Examples 23 to 31.
  • FIG. 10 is a graph showing changes in ⁇ -type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation temperature of the second fluid in Examples 23 to 31.
  • FIG. 4 is a graph showing the change in crystallinity / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid in Examples 32 to 40.
  • 40 is a graph showing changes in ⁇ -type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid in Examples 32 to 40.
  • 4 is a graph showing the change in crystallinity / average particle diameter of PR122 fine particles with respect to the preparation temperature of the second fluid in Examples 32 to 40.
  • FIG. 40 is a graph showing changes in ⁇ -type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation temperature of the second fluid in Examples 32 to 40.
  • FIG. 6 is a graph showing changes in crystallinity / average particle diameter of indomethacin fine particles with respect to the preparation time of the second fluid in Examples 41 to 49.
  • FIG. FIG. 6 is a graph showing changes in crystallinity / average particle diameter of indomethacin fine particles with respect to the preparation temperature of the second fluid in Examples 41 to 49.
  • FIG. FIG. 6 is a graph showing changes in ⁇ -type crystal ratio / average particle diameter of indomethacin fine particles with respect to the preparation time of the second fluid in Examples 41 to 49.
  • FIG. FIG. 10 is a graph showing changes in indomethacin fine particle ⁇ -type crystal ratio / average particle diameter with respect to the preparation temperature of the second fluid in Examples 41 to 49.
  • the type of fine particles in the present invention is not particularly limited, and examples thereof include organic substances, inorganic substances, and organic-inorganic composites. Other examples include metals and / or non-metals and compounds thereof. Although it does not specifically limit as a metal and / or a nonmetallic compound, For example, a metal or a nonmetallic salt, an oxide, a hydroxide, a hydroxide oxide, a nitride, a carbide, a complex, an organic salt, an organic Complexes, organic compounds or their hydrates, organic solvates and the like can be mentioned.
  • metal or non-metal nitrates and nitrites, sulfates and sulfites, formates and acetates, phosphates and phosphites, hypophosphites and chlorides, oxy salts and acetylacetates examples thereof include narate salts, hydrates thereof, and organic solvates.
  • an anti-solvent method for precipitating, precipitating or crystallizing the fine particles a reaction such as an oxidation reaction, a reduction reaction, and the like, which are arranged to face each other, can be approached and separated, and at least one is on the other side.
  • a reaction such as an oxidation reaction, a reduction reaction, and the like
  • fine particles can be produced.
  • a fine particle raw material solution obtained by mixing or dissolving a fine particle raw material that is a target fine particle raw material in a solvent, and a precipitation solvent for precipitating the fine particle raw material from the fine particle raw material solution are arranged to face each other.
  • the fine particle raw material in the present invention the same fine particles as those mentioned above can be used.
  • the fine particle material solution in the present invention is obtained by mixing or dissolving (hereinafter simply referred to as dissolution) at least one kind of fine particle material in a solvent. Desirably, it is carried out by dissolving or dispersing at least one kind of fine particle raw material in a solvent.
  • the pigment is used as the raw material for fine particles in the present invention, it is not particularly limited.
  • organic pigments inorganic pigments, organic-inorganic composite pigments, all pigments registered in The Society of Dyers and Colorists, etc. Can be mentioned.
  • the organic pigment in the present invention is not particularly limited, but for example, perylene compound pigment, perinone compound pigment, quinacridone compound pigment, quinacridone quinone compound pigment, anthraquinone compound pigment, anthanthrone compound pigment, benzimidazolone compound pigment, Disazo condensation compound pigment, disazo compound pigment, azo compound pigment, indanthrone compound pigment, phthalocyanine compound pigment, triarylcarbonium compound pigment, dioxazine compound pigment, aminoanthraquinone compound pigment, thioindigo compound pigment, isoindoline compound pigment, isoindolinone Compound pigments, pyranthrone compound pigments, isoviolanthrone compound pigments, or mixtures thereof.
  • the inorganic pigment in the present invention is not particularly limited, and examples thereof include metal compounds. Although not particularly limited, bengara, black iron oxide, yellow iron oxide compounds, titanium oxide and zinc oxide as white pigments, bitumen, ultramarine, chromium oxide, magnesium oxide and aluminum oxide, calcium oxide, zirconium oxide, cadmium and zinc All metal compounds such as sulfides, other inorganic color pigments and inorganic compounds in general.
  • Examples of the solvent for dissolving the fine particle raw material include water, an organic solvent, or a mixed solvent composed of a plurality of them.
  • Examples of the water include tap water, ion-exchanged water, pure water, ultrapure water, and RO water.
  • Examples of the organic solvent include alcohol solvents, amide solvents, ketone solvents, ether solvents, aromatic solvents.
  • Examples include solvents, carbon disulfide, aliphatic solvents, nitrile solvents, sulfoxide solvents, halogen solvents, ester solvents, ionic liquids, carboxylic acid compounds, and sulfonic acid compounds. Each of the above solvents may be used alone or in combination of two or more.
  • the present invention can also be carried out by mixing or dissolving a basic substance or an acidic substance in the solvent.
  • basic substances include metal hydroxides such as sodium hydroxide and potassium hydroxide, metal alkoxides such as sodium methoxide and sodium isopropoxide, and amine compounds such as triethylamine, 2-diethylaminoethanol and diethylamine. Can be mentioned.
  • acidic substances include inorganic acids such as aqua regia, hydrochloric acid, nitric acid, fuming nitric acid, sulfuric acid and fuming sulfuric acid, and organic acids such as formic acid, acetic acid, chloroacetic acid, dichloroacetic acid, oxalic acid, trifluoroacetic acid and trichloroacetic acid. It is done.
  • These basic substances or acidic substances can be carried out by mixing with various solvents as described above, or can be used alone.
  • an oxidizing agent or a reducing agent in the solvent.
  • an oxidizing agent Nitrate, hypochlorite, permanganate, and a peroxide are mentioned.
  • the reducing agent include lithium aluminum hydride and sodium borohydride, hydrazine and hydrazine hydrate, sulfite, metal ions, particularly transition metal ions (iron ions, titanium ions, etc.).
  • the same solvent as the above solvent can be used.
  • the solvent for dissolving the fine particle raw material and the solvent for precipitation can be carried out by selecting a solvent for dissolving the target fine particles and a solvent for precipitation.
  • the fine particle raw material solution is preferably prepared using a stirrer having a rotating stirring blade.
  • a stirrer having a rotating stirring blade is used.
  • a fine particle raw material solution can be rapidly produced.
  • the preparation of the fine particle raw material solution is performed using a stirrer having a rotating agitating blade to obtain a uniform molecular level.
  • the inventor presumes that a fine particle raw material solution in a dissolved state or a molecular dispersion state can be obtained, and that the dissolved state and the cluster formation state of the fine particle raw material solution can be improved.
  • the inventor changed the various conditions of the stirrer while repeating trial and error to prepare a fine particle raw material solution, and the prepared fine particle raw material solution and the precipitation solvent are arranged to face each other and can be approached and separated.
  • the stirring energy is increased by changing the conditions of the stirrer.
  • the ratio of crystallinity to the particle diameter of the precipitated fine particles can be controlled to increase.
  • the ratio of the composition ratio of the specific crystal type to the particle size of the precipitated fine particles is increased by increasing the stirring energy by changing the conditions of the stirrer. It can be controlled to rise.
  • the ratio of crystallinity to the particle diameter of the precipitated fine particles is increased by increasing the stirring energy by changing various conditions of the stirrer.
  • the ratio of the composition ratio of the specific crystal type to the particle size of the precipitated fine particles is increased by increasing the stirring energy by changing the conditions of the stirrer. Can be controlled to rise.
  • the stirring time using the stirrer having the above is not limited.
  • the stirrer in the present invention is not particularly limited as long as it is a stirrer having a rotating stirring blade, but in a general stirrer having a rotating stirring blade, the peripheral speed at the tip of the stirring blade is 1 m / sec or more. Is said to be high-speed rotation.
  • the stirring method is not particularly limited, but it can be carried out using various shearing type, friction type, high pressure jet type, ultrasonic type stirring machines, dissolving machines, emulsifying machines, dispersing machines, homogenizers and the like.
  • Examples include continuous emulsifiers such as Ultra Turrax (manufactured by IKA), TK homomixer (manufactured by Primics), TK homomic line flow, fill mix (both by Primics), Claremix (M And batch-type or continuous-use emulsifiers such as Technic Co., Ltd. and Claremix Dissolver (M Technic Co., Ltd.).
  • the fine particle raw material solution may be prepared using an ultrasonic homogenizer, an ultrasonic cleaner, a high-pressure homogenizer, or the like.
  • the stirrer having a rotating stirring blade can be used in various forms.
  • a stirring chamber having a screen having a plurality of discharge ports A stirrer that includes a stirring blade that rotates in the stirring chamber and that is configured so that the tip of the stirring blade rotates with a small distance from the inner surface of the screen can be shown.
  • the screen and the stirring blade are only required to rotate relatively, and the screen may be rotated in the direction opposite to the rotation direction of the stirring blade, or may be fixed and not rotated.
  • the stirrer according to this embodiment will be described in more detail with reference to FIG. 4 and FIG. As shown in FIG. 4, the stirrer having the rotating stirring blade is inserted through the lid 102 into the storage tank 101 that stores the fluid to be processed.
  • the stirrer having the rotating stirring blade includes a stirring chamber 103 and a support cylinder 104 that supports the stirring chamber 103.
  • An impeller 105 is accommodated in the stirring chamber 103.
  • the impeller 105 is provided at the tip of the rotation shaft 106, and the rotation shaft 106 is disposed inside the support cylinder 104.
  • the rotating shaft 106 and the impeller 105 rotate in the opposite direction with respect to the support cylinder 104 and the stirring chamber 103.
  • the base ends of the support cylinder 104 and the rotation shaft 106 are connected to separate rotation driving means (not shown).
  • the stirring chamber 103 includes a housing 121 provided at the front end of the support cylinder 104 and a screen 122 provided at the front end side of the housing 121.
  • a suction port 123 is formed in the housing 121, and a discharge port 125 is formed in the screen 122.
  • the fluid to be processed is guided from the suction port 123 into the stirring chamber 103 by the rotation of the impeller 105, and after the processing such as dispersion and dissolution, the fluid to be processed is discharged from the discharge port 125 to the outside.
  • the discharge port 125 may be used as the suction port, and the suction port 123 may be used as the discharge port.
  • the partition 124 can be provided, but can also be implemented without providing it.
  • the tip of the blade 107 of the impeller 105 runs along the inner wall of the screen 122 with a small interval.
  • This minute interval is preferably set to about 0.2 to 2 mm, and a large shearing force is applied to the fluid to be treated in this minute gap, and the fluid to be treated is caused by the rotation of the impeller 105.
  • Kinetic energy is given to the body, and the pressure of the fluid to be treated is increased in front of the rotation direction of the blades 107.
  • This high-pressure fluid to be treated passes through the discharge port 125, and is further accelerated. Are discharged to the outside of the screen 122.
  • the pressure is negative behind the rotation direction of the blade 107, and the fluid to be processed is sucked into the screen 122 from the discharge port 125 immediately after the blade 107 passes through the discharge port 125.
  • a shear force is generated between the fluids to be treated due to the reverse flow of the fluids to be treated.
  • the above action is achieved by relatively rotating the stirring chamber 103 having the screen 122 and the impeller 105. Specifically, it can be obtained by rotating the blade 107 as a stirring blade inside the stirring chamber 103 in a stationary state. Further, as in the above-described example, the discharge port 125 can be rotated in the direction opposite to the rotation direction of the impeller 105 by rotating the stirring chamber 103 and the impeller 105 in the opposite directions. .
  • the present invention is not limited to this, and the screen 122 having the discharge port 125 may be removed, and only the housing 121 having the suction port 123 may be provided and rotated. By removing the screen 122, the fluid to be treated can be dissolved in a short time while performing cavitation control without applying a shearing force to the fluid to be treated. However, it is preferable to provide the screen 122 on the front end side of the housing 121 because an intermittent jet flow is generated.
  • the fluid to be processed is sheared in a minute gap between the inner wall of the screen 122 including the discharge port 125 and the tip of the blade 107, and The fluid to be processed is discharged from the inside to the outside of the screen 122 as an intermittent jet flow through the discharge port 125.
  • the intermittent jet flow effectively acts on the dissolution of the fine particle raw material in the solvent, and the fine particle raw material solution has a molecular level dissolved state or molecular dispersed state.
  • one or both of the suction port 123 and the discharge port 125 provided in the stirring chamber 103 rotate, so that the fluid to be processed is sucked or discharged or discharged from the fluid to be processed outside the stirring chamber 103. Both the positions are sequentially changed, and the generation of the fluid to be treated that is excluded from the circulation can be prevented.
  • the agitation chamber 103 may be omitted, and only the impeller 105 may be exposed and rotated.
  • an introduction fin 131 that is spirally wound along the longitudinal direction of the support cylinder 104 may be provided.
  • the introduction fin 131 rotates in the same body as the support cylinder 104, the fluid to be processed located in the upper part of the storage tank 101 descends along the outer periphery of the support cylinder 104 and is guided to the suction port 123. It is also possible to provide a circulation fin 132 wound in the opposite direction to the introduction fin 131.
  • the circulation fins 132 are arranged outside the introduction fins 131 and circulate the fluid to be processed discharged from the discharge ports 125 upward of the storage tank 101.
  • the stirrer shown by FIG.4 and FIG.5 is commercialized as the above-mentioned Clare mix (made by M technique Co., Ltd.).
  • the blades 107 of the impeller 105 may extend linearly from the center of the impeller 105 with a certain width in a cross section (cross section orthogonal to the axial direction of the rotating shaft 106), and go outward. Accordingly, the width may be gradually increased, or may be extended outward while being curved. Further, in the axial direction of the rotating shaft 106, these blades 107 may extend linearly along a plane including the rotating shaft of the rotating shaft 106, and bend in a vertical direction such as a spiral shape. It may extend. Further, the maximum outer diameter of the blade 107 of the impeller 105 can be appropriately set according to the embodiment.
  • the discharge port 125 is illustrated as extending linearly in the axial direction of the rotation shaft 106 (vertical direction in the example in the figure), it may be curved and extended such as a spiral shape. Further, the shape of the discharge port 125 is not necessarily an elongated space, and may be a polygon, a circle, an ellipse, or the like. In the circumferential direction, a plurality of discharge ports 125 are formed at equal intervals. However, the discharge ports 125 may be formed at different intervals, and may prevent the discharge ports 125 having a plurality of types and sizes from being provided. Absent.
  • this invention is not limited to what uses the said Clare mix and a Clare mix dissolver, It can also implement using the stirrer which has a general stirring blade.
  • the peripheral speed of the stirring blade when dissolving the fine particle raw material in the solvent is not particularly limited, but is preferably 1 m / sec or more. It can be properly used depending on the viscosity and temperature of the solvent or the concentration of the fine particle raw material to be dissolved.
  • the peripheral speed of the stirring blade means a moving speed in the maximum outer diameter portion of the stirring blade, and is specifically calculated from the following equation.
  • r is the maximum radius of the stirring blade
  • ⁇ is the angular velocity
  • f is the rotational speed of the stirring blade per unit time
  • ⁇ is the circumference.
  • the same energy is used to change the various conditions (stirring time, peripheral speed of the stirring blade, temperature of the fine particle raw material solution) to increase or decrease the stirring energy. If a fine particle raw material solution in a dissolved state or a molecular dispersion state is obtained and the properties / characteristics of the fine particles deposited by mixing the fine particle raw material solution and the precipitation solvent in the thin film fluid can be controlled, a plurality of devices may be used. The stirring energy may be increased or decreased by changing these conditions. *
  • the other conditions of the stirrer may be changed. For example, by changing the combination of the shape of the blade 107 of the impeller 105 of FIG. 4 and FIG. 5 and the shape of the discharge port 125 of the screen 122, the fine particle raw material solution that is dissolved or dispersed in the molecular level. You might get.
  • a blade 107 that curves and extends in a direction opposite to the rotation direction of the rotation shaft 106 as it moves away from the rotation shaft 106, or (B) a blade 107 that extends linearly in the radial direction of the rotation shaft, (C)
  • the 1 mm wide discharge port 125 has 24 screens 122 or (D) the 2 mm wide discharge port 125 has 24 screens 122, and the dissolved state or molecular dispersion at the molecular level can be changed by changing the combination.
  • the properties / characteristics of the fine particles deposited can be controlled by obtaining the fine particle raw material solution in a state and then mixing the fine particle raw material solution and the precipitation solvent in the thin film fluid.
  • the fluid processing apparatus shown in FIGS. 1 to 3 is the same as the apparatus described in Patent Document 3, and between the processing surfaces in the processing unit in which at least one of which can be approached / separated rotates relative to the other.
  • the first fluid, which is the first fluid to be treated, of the fluids to be treated is introduced between the processing surfaces and is independent of the flow path into which the fluid is introduced.
  • the second fluid which is the second fluid to be processed, is introduced between the processing surfaces from another flow path having an opening communicating between the processing surfaces.
  • the first fluid and the second fluid are mixed and stirred.
  • U indicates the upper side
  • S indicates the lower side.
  • the upper, lower, front, rear, left and right only indicate a relative positional relationship, and do not specify an absolute position.
  • R indicates the direction of rotation.
  • C indicates the centrifugal force direction (radial direction).
  • This apparatus uses at least two kinds of fluids as a fluid to be treated, and at least one kind of fluid includes at least one kind of an object to be treated and is opposed to each other so as to be able to approach and separate.
  • a processing surface that is disposed and at least one of which rotates relative to the other, and combines the fluids between the processing surfaces to form a thin film fluid.
  • This fluid processing apparatus includes first and second processing units 10 and 20 that face each other, and at least one of the processing units rotates.
  • the opposing surfaces of both processing parts 10 and 20 are processing surfaces.
  • the first processing unit 10 includes a first processing surface 1
  • the second processing unit 20 includes a second processing surface 2.
  • Both the processing surfaces 1 and 2 are connected to the flow path of the fluid to be processed and constitute a part of the flow path of the fluid to be processed.
  • the distance between the processing surfaces 1 and 2 can be changed as appropriate, but is usually adjusted to 1 mm or less, for example, a minute distance of about 0.1 ⁇ m to 50 ⁇ m.
  • the fluid to be processed that passes between the processing surfaces 1 and 2 becomes a forced thin film fluid forced by the processing surfaces 1 and 2.
  • the apparatus When a plurality of fluids to be processed are processed using this apparatus, the apparatus is connected to the flow path of the first fluid to be processed and forms a part of the flow path of the first fluid to be processed. At the same time, a part of the flow path of the second fluid to be treated is formed separately from the first fluid to be treated. And this apparatus performs processing of fluid, such as making both flow paths merge and mixing both the to-be-processed fluids between the processing surfaces 1 and 2, and making it react.
  • “treatment” is not limited to a form in which the object to be treated reacts, but also includes a form in which only mixing and dispersion are performed without any reaction.
  • the first holder 11 that holds the first processing portion 10 the second holder 21 that holds the second processing portion 20, a contact pressure application mechanism, a rotation drive mechanism, A first introduction part d1, a second introduction part d2, and a fluid pressure imparting mechanism p are provided.
  • the first processing portion 10 is an annular body, more specifically, a ring-shaped disk.
  • the second processing unit 20 is also a ring-shaped disk.
  • the first and second processing parts 10 and 20 are made of metal, ceramic, sintered metal, wear-resistant steel, sapphire, other metals subjected to hardening treatment, hard material lining or coating, It is possible to adopt a material with plating applied.
  • at least a part of the first and second processing surfaces 1 and 2 facing each other is mirror-polished in the processing units 10 and 20.
  • the surface roughness of this mirror polishing is not particularly limited, but is preferably Ra 0.01 to 1.0 ⁇ m, more preferably Ra 0.03 to 0.3 ⁇ m.
  • At least one of the holders can be rotated relative to the other holder by a rotational drive mechanism (not shown) such as an electric motor.
  • Reference numeral 50 in FIG. 1 denotes a rotation shaft of the rotation drive mechanism.
  • the first holder 11 attached to the rotation shaft 50 rotates and is used for the first processing supported by the first holder 11.
  • the unit 10 rotates with respect to the second processing unit 20.
  • the second processing unit 20 may be rotated, or both may be rotated.
  • the first and second holders 11 and 21 are fixed, and the first and second processing parts 10 and 20 are rotated with respect to the first and second holders 11 and 21. May be.
  • At least one of the first processing unit 10 and the second processing unit 20 can be approached / separated from at least either one, and both processing surfaces 1 and 2 can be approached / separated. .
  • the second processing unit 20 approaches and separates from the first processing unit 10, and the second processing unit 20 is disposed in the storage unit 41 provided in the second holder 21. It is housed in a hauntable manner.
  • the first processing unit 10 may approach or separate from the second processing unit 20, and both the processing units 10 and 20 may approach or separate from each other. It may be a thing.
  • the accommodating portion 41 is a recess that mainly accommodates a portion of the second processing portion 20 on the side opposite to the processing surface 2 side, and is a groove that has a circular shape, that is, is formed in an annular shape in plan view. .
  • the accommodating portion 41 accommodates the second processing portion 20 with a sufficient clearance that allows the second processing portion 20 to rotate.
  • the second processing unit 20 may be arranged so that only the parallel movement is possible in the axial direction, but by increasing the clearance, the second processing unit 20 is
  • the center line of the processing unit 20 may be displaced by being inclined so as to break the relationship parallel to the axial direction of the storage unit 41. Furthermore, the center line of the second processing unit 20 and the storage unit 41 may be displaced. The center line may be displaced so as to deviate in the radial direction. As described above, it is desirable to hold the second processing unit 20 by the floating mechanism that holds the three-dimensionally displaceably.
  • the above-described fluid to be treated is subjected to both treatment surfaces from the first introduction part d1 and the second introduction part d2 in a state where pressure is applied by a fluid pressure application mechanism p configured by various pumps and potential energy. It is introduced between 1 and 2.
  • the first introduction part d1 is a passage provided in the center of the annular second holder 21, and one end of the first introduction part d1 is formed on both processing surfaces from the inside of the annular processing parts 10, 20. It is introduced between 1 and 2.
  • the second introduction part d2 supplies the second processing fluid to be reacted with the first processing fluid to the processing surfaces 1 and 2.
  • the second introduction part d ⁇ b> 2 is a passage provided inside the second processing part 20, and one end thereof opens at the second processing surface 2.
  • the first fluid to be processed that has been pressurized by the fluid pressure imparting mechanism p is introduced from the first introduction part d1 into the space inside the processing parts 10 and 20, and the first processing surface 1 and the second processing surface 2 are supplied. It passes between the processing surfaces 2 and tries to pass outside the processing portions 10 and 20. Between these processing surfaces 1 and 2, the second fluid to be treated pressurized by the fluid pressure applying mechanism p is supplied from the second introduction part d 2, merged with the first fluid to be treated, and mixed.
  • the contact surface pressure applying mechanism applies to the processing portion a force that causes the first processing surface 1 and the second processing surface 2 to approach each other.
  • the contact pressure applying mechanism is provided in the second holder 21 and biases the second processing portion 20 toward the first processing portion 10.
  • the contact surface pressure applying mechanism is a force that pushes in a direction in which the first processing surface 1 of the first processing unit 10 and the second processing surface 2 of the second processing unit 20 approach (hereinafter referred to as contact pressure). It is a mechanism for generating.
  • a thin film fluid having a minute film thickness of nm to ⁇ m is generated by the balance between the contact pressure and the force for separating the processing surfaces 1 and 2 such as fluid pressure. In other words, the distance between the processing surfaces 1 and 2 is kept at a predetermined minute distance by the balance of the forces.
  • the contact surface pressure applying mechanism is arranged between the accommodating portion 41 and the second processing portion 20.
  • a spring 43 that biases the second processing portion 20 in a direction approaching the first processing portion 10 and a biasing fluid introduction portion 44 that introduces a biasing fluid such as air or oil.
  • the contact surface pressure is applied by the spring 43 and the fluid pressure of the biasing fluid. Any one of the spring 43 and the fluid pressure of the urging fluid may be applied, and other force such as magnetic force or gravity may be used.
  • the second processing unit 20 causes the first treatment by the separation force generated by the pressure or viscosity of the fluid to be treated which is pressurized by the fluid pressure imparting mechanism p against the bias of the contact surface pressure imparting mechanism.
  • the first processing surface 1 and the second processing surface 2 are set with an accuracy of ⁇ m by the balance between the contact surface pressure and the separation force, and a minute amount between the processing surfaces 1 and 2 is set. An interval is set.
  • the separation force includes the fluid pressure and viscosity of the fluid to be processed, the centrifugal force due to the rotation of the processing portion, the negative pressure when the urging fluid introduction portion 44 is negatively applied, and the spring 43 being pulled.
  • the force of the spring when it is used as a spring can be mentioned.
  • This contact surface pressure imparting mechanism may be provided not in the second processing unit 20 but in the first processing unit 10 or in both.
  • the separation force will be specifically described.
  • the second processing unit 20 is arranged inside the second processing surface 2 together with the second processing surface 2 (that is, the first processing surface 1 and the second processing surface 2).
  • a separation adjusting surface 23 is provided adjacent to the second processing surface 2 and located on the entrance side of the fluid to be processed between the processing surface 2 and the processing surface 2.
  • the separation adjusting surface 23 is implemented as an inclined surface, but may be a horizontal surface.
  • the pressure of the fluid to be processed acts on the separation adjusting surface 23 to generate a force in a direction in which the second processing unit 20 is separated from the first processing unit 10. Accordingly, the pressure receiving surfaces for generating the separation force are the second processing surface 2 and the separation adjusting surface 23.
  • the proximity adjustment surface 24 is formed on the second processing portion 20.
  • the proximity adjustment surface 24 is a surface opposite to the separation adjustment surface 23 in the axial direction (upper surface in FIG. 1), and the pressure of the fluid to be processed acts on the second processing portion 20. A force is generated in a direction that causes the first processing unit 10 to approach the first processing unit 10.
  • the pressure of the fluid to be processed that acts on the second processing surface 2 and the separation adjusting surface 23, that is, the fluid pressure, is understood as a force constituting an opening force in the mechanical seal.
  • the projected area A1 of the proximity adjustment surface 24 projected on a virtual plane orthogonal to the approaching / separating direction of the processing surfaces 1 and 2, that is, the protruding and protruding direction (axial direction in FIG. 1) of the second processing unit 20 The area ratio A1 / A2 of the total area A2 of the projected areas of the second processing surface 2 and the separation adjusting surface 23 of the second processing unit 20 projected onto the virtual plane is called a balance ratio K. This is important for adjusting the opening force.
  • the opening force can be adjusted by changing the balance line, that is, the area A1 of the adjustment surface 24 for proximity, by the pressure of the fluid to be processed, that is, the fluid pressure.
  • P1 represents the pressure of the fluid to be treated, that is, the fluid pressure
  • K represents the balance ratio
  • k represents the opening force coefficient
  • Ps represents the spring and back pressure
  • the proximity adjustment surface 24 may be implemented with a larger area than the separation adjustment surface 23.
  • the fluid to be processed becomes a thin film fluid forced by the two processing surfaces 1 and 2 holding the minute gaps, and tends to move to the outside of the two annular processing surfaces 1 and 2.
  • the mixed fluid to be processed does not move linearly from the inside to the outside of the two processing surfaces 1 and 2, but instead has an annular radius.
  • a combined vector of the movement vector in the direction and the movement vector in the circumferential direction acts on the fluid to be processed and moves in a substantially spiral shape from the inside to the outside.
  • the rotating shaft 50 is not limited to a vertically arranged shaft, and may be arranged in the horizontal direction, or may be arranged in an inclined manner. This is because the fluid to be processed is processed at a fine interval between the processing surfaces 1 and 2 and the influence of gravity can be substantially eliminated. Further, this contact surface pressure applying mechanism also functions as a buffer mechanism for fine vibration and rotational alignment when used in combination with a floating mechanism that holds the second processing portion 20 in a displaceable manner.
  • At least one of the first and second processing parts 10 and 20 may be cooled or heated to adjust the temperature.
  • the first and second processing parts 10 and 10 are adjusted.
  • 20 are provided with temperature control mechanisms (temperature control mechanisms) J1, J2.
  • the temperature of the introduced fluid to be treated may be adjusted by cooling or heating. These temperatures can also be used for the deposition of the treated material, and also to generate Benard convection or Marangoni convection in the fluid to be treated between the first and second processing surfaces 1 and 2. May be set.
  • a groove-like recess 13 extending from the center side of the first processing portion 10 to the outside, that is, in the radial direction is formed on the first processing surface 1 of the first processing portion 10. May be implemented.
  • the planar shape of the recess 13 is curved or spirally extending on the first processing surface 1, or is not shown, but extends straight outward, L It may be bent or curved into a letter shape or the like, continuous, intermittent, or branched.
  • the recess 13 can be implemented as one formed on the second processing surface 2, and can also be implemented as one formed on both the first and second processing surfaces 1, 2.
  • the base end of the recess 13 reaches the inner periphery of the first processing unit 10.
  • the tip of the recess 13 extends toward the outer peripheral surface of the first processing surface 1, and the depth (cross-sectional area) gradually decreases from the base end toward the tip.
  • a flat surface 16 without the recess 13 is provided between the tip of the recess 13 and the outer peripheral surface of the first processing surface 1.
  • the opening d20 of the second introduction part d2 is provided in the second processing surface 2, it is preferably provided at a position facing the flat surface 16 of the opposing first processing surface 1.
  • the opening d20 is desirably provided on the downstream side (outside in this example) from the concave portion 13 of the first processing surface 1.
  • it is installed at a position facing the flat surface 16 on the outer diameter side from the point where the flow direction when introduced by the micropump effect is converted into a laminar flow direction in a spiral shape formed between the processing surfaces. It is desirable to do.
  • the distance n in the radial direction from the outermost position of the recess 13 provided in the first processing surface 1 is preferably about 0.5 mm or more.
  • the shape of the opening d20 may be circular as shown in FIGS. 2B and 3B, and although not shown, a concentric circle surrounding the central opening of the processing surface 2 that is a ring-shaped disk.
  • An annular shape may be used.
  • the annular opening may be continuous or discontinuous.
  • the shape of the opening is a concentric ring shape.
  • the second introduction part d2 can have directionality.
  • the introduction direction from the opening d20 of the second processing surface 2 is inclined with respect to the second processing surface 2 at a predetermined elevation angle ( ⁇ 1).
  • the elevation angle ( ⁇ 1) is set to be more than 0 degrees and less than 90 degrees, and in the case of a reaction with a higher reaction rate, it is preferably set at 1 to 45 degrees.
  • the introduction direction from the opening d20 of the second processing surface 2 has directionality in the plane along the second processing surface 2.
  • the introduction direction of the second fluid is a component in the radial direction of the processing surface that is an outward direction away from the center and a component with respect to the rotation direction of the fluid between the rotating processing surfaces. Is forward.
  • a line segment in the radial direction passing through the opening d20 and extending outward is defined as a reference line g and has a predetermined angle ( ⁇ 2) from the reference line g to the rotation direction R. This angle ( ⁇ 2) is also preferably set to more than 0 degree and less than 90 degrees.
  • This angle ( ⁇ 2) can be changed and implemented in accordance with various conditions such as the type of fluid, reaction speed, viscosity, and rotational speed of the processing surface.
  • the second introduction part d2 may not have any directionality.
  • the number of fluids to be treated and the number of flow paths are two, but may be one, or may be three or more.
  • the second fluid is introduced between the processing surfaces 1 and 2 from the second introduction part d2, but this introduction part may be provided in the first processing part 10 or provided in both. Good. Moreover, you may prepare several introduction parts with respect to one type of to-be-processed fluid.
  • the shape, size, and number of the opening for introduction provided in each processing portion are not particularly limited, and can be appropriately changed. An opening for introduction may be provided immediately before or between the first and second processing surfaces 1 and 2 or further upstream.
  • the second fluid is introduced from the first introduction part d1 and the first fluid is introduced from the second introduction part d2, contrary to the above. May be introduced.
  • the expressions “first” and “second” in each fluid have only an implication for identification that they are the nth of a plurality of fluids, and a third or higher fluid may exist.
  • processes such as precipitation / precipitation or crystallization are disposed so as to be able to approach and separate from each other, and at least one of the processing surfaces 1 rotates with respect to the other. Occurs with forcible uniform mixing between the two.
  • the particle size and monodispersity of the processed material to be processed are the rotational speed and flow velocity of the processing parts 10 and 20, the distance between the processing surfaces 1 and 2, the raw material concentration of the processed fluid, or the processed fluid. It can be controlled by appropriately adjusting the solvent species and the like.
  • At least one kind of fine particle raw material solution in which at least one kind of fine particle raw material is dissolved in a solvent and at least one kind of precipitation solvent are arranged to face each other, and at least one of them is the other. It introduce
  • the fine particle raw material solution is prepared using a stirrer having a rotating stirring blade, and at least one of three conditions (stirring time, peripheral speed of the stirring blade, and temperature of the fine particle raw material solution) for defining the stirring energy.
  • the stirring energy is increased or decreased by changing.
  • the fine particle precipitation reaction of the apparatus shown in FIG. 1 of the present application is forcibly arranged between the processing surfaces 1 and 2 which are arranged so as to be able to approach and separate from each other and at least one rotates with respect to the other. Occurs with uniform mixing.
  • a fine particle material solution obtained by dissolving at least one kind of fine particle material in a solvent as a second fluid is applied to the first fluid film formed between the processing surfaces 1 and 2 from the second introduction part d2 which is a separate channel. Install directly.
  • the first fluid and the second fluid are disposed between the processing surfaces 1 and 2 whose distance is fixed by the pressure balance between the supply pressure of the fluid to be processed and the pressure applied between the rotating processing surfaces. Can be mixed to perform precipitation reaction of fine particles.
  • the second fluid is introduced from the first introduction part d1 and the first fluid is introduced from the second introduction part d2, contrary to the above. May be introduced.
  • the expressions “first” and “second” in each fluid have only an implication for identification that they are the nth of a plurality of fluids, and a third or higher fluid may exist.
  • the third introduction part d3 can be provided in the processing apparatus.
  • the first fluid, the first fluid is supplied from each introduction part.
  • a third fluid different from the two fluids, the first fluid, and the second fluid can be separately introduced into the processing apparatus. If it does so, the density
  • the combination of fluids to be processed (first fluid to third fluid) to be introduced into each introduction portion can be arbitrarily set. The same applies to the case where the fourth or more introduction portions are provided, and the fluid to be introduced into the processing apparatus can be subdivided in this way.
  • the temperature of the fluid to be processed such as the first and second fluids is controlled, and the temperature difference between the first fluid and the second fluid (that is, the temperature difference between the supplied fluids to be processed) is controlled.
  • the temperature of each processed fluid processing device, more specifically, the temperature immediately before being introduced between the processing surfaces 1 and 2 is measured. It is also possible to add a mechanism for heating or cooling each fluid to be processed introduced between the processing surfaces 1 and 2.
  • the pigment fine particle precipitation reaction described below occurs while being forcibly and uniformly mixed between the processing surfaces 1 and 2 which are disposed so as to be able to approach and separate from each other and at least one rotates relative to the other.
  • Control of the particle size and monodispersity of the pigment fine particles, and the type of crystal type can be adjusted by changing the rotational speed, flow rate, distance between processing surfaces, raw material concentration, etc. of the processing units 10 and 20. it can.
  • This point is as pointed out by the present applicant in Patent 4916698 and the like, and the present applicant emphasizes the precipitation step and adjusts the rotation speed, flow rate, and distance between the processing surfaces. We have been working on the production of fine particles with the desired physical properties and performance.
  • the present invention has been completed. This makes it possible to change the crystallinity and crystal form of the fine particles by changing the conditions of the dissolution step while fixing the conditions of the precipitation step, and to obtain the properties and performance of the desired fine particles. By changing the conditions of both the precipitation step and the precipitation step, the properties and performance of the target fine particles can be changed more dynamically.
  • pigment fine particle precipitation reaction acid pasting is obtained by dissolving the pigment bulk powder in a strong acid such as sulfuric acid, nitric acid, hydrochloric acid, etc., and mixing the prepared pigment acidic solution with a solution containing water or an organic solvent.
  • Alkali paste method, reprecipitation method, pH adjustment method, anti-solvent method to obtain pigment fine particles by dissolving the method and pigment powder in an alkali solution and mixing the prepared pigment alkali solution with a solution containing water or an organic solvent
  • Various liquid phase methods such as can be used.
  • These precipitation reactions can be carried out by a conventionally known method as described in Patent Document 3, for example.
  • the reaction of producing pigment fine particles using the above apparatus will be described in more detail.
  • a solution containing water or an organic solvent as a first fluid is disposed opposite to each other so as to be able to approach and separate from the first introduction part d1 which is one flow path.
  • a thin film fluid composed of a first fluid is formed between the processing surfaces 1 and 2 between the processing surfaces 1 and 2 that are provided and at least one rotates with respect to the other.
  • a fluid (pigment acid solution) containing an acid in which a pigment substance as a reactant is dissolved as a second fluid is directly applied to the thin film fluid composed of the first fluid.
  • the first fluid and the second fluid exceed each other between the processing surfaces 1 and 2 whose distance is fixed by the pressure balance between the fluid supply pressure and the pressure applied between the rotating processing surfaces. While maintaining the thin film state, it is possible to carry out a reaction that is instantaneously mixed to produce pigment fine particles.
  • the second fluid is introduced from the first introduction part d1 and the first fluid is introduced from the second introduction part d2, contrary to the above. May be introduced.
  • the expressions “first” and “second” in each solvent only have a meaning for identification that they are the n-th of a plurality of solvents, and third or more solvents may exist.
  • the first fluid is water or a solution containing an organic solvent.
  • the water is preferably purified water such as ion exchange water, pure water, or distilled water.
  • Methanol, ethanol, or propanol may be used.
  • the acid used in the second fluid is not particularly limited as long as it shows solubility in the pigment and is not particularly limited.
  • sulfuric acid, hydrochloric acid, nitric acid, and trifluoroacetic acid can be used.
  • a strong acid, particularly 95% or more of concentrated sulfuric acid can be used.
  • an organic solvent may be mixed with the first fluid or the second fluid for the purpose of controlling the crystal type of the pigment or controlling the quality of the pigment.
  • organic solvents can be used.
  • a dispersant such as a block copolymer, a polymer, or a surfactant may be included.
  • a fluid containing an organic solvent in which a pigment substance is dissolved as a second fluid is directly introduced into the thin film fluid composed of the first fluid from the second introduction part d2 which is a separate flow path.
  • the first fluid and the second fluid are ultrathin between the processing surfaces 1 and 2 that are fixed in distance by the pressure balance between the fluid supply pressure and the pressure applied between the processing surfaces 1 and 2. While maintaining the state, it is possible to carry out a reaction that is instantaneously mixed to produce pigment fine particles.
  • the second fluid is introduced from the first introduction part d1 and the first fluid is introduced from the second introduction part d2, contrary to the above. May be introduced.
  • the expressions “first” and “second” in each solvent only have a meaning for identification that they are the n-th of a plurality of solvents, and third or more solvents may exist.
  • the first fluid is not particularly limited as long as it is compatible with the solvent that dissolves the pigment that forms the second fluid with a poor solvent for the pigment, but water, alcohol solvents, ketone solvents, ether solvents Solvent, aromatic solvent, carbon disulfide, aliphatic solvent, nitrile solvent, sulfoxide solvent, halogen solvent, ester solvent, ionic liquid, or a mixture of two or more of these preferable.
  • the organic solvent used in the second fluid is not particularly limited as long as it shows solubility in pigments, but is preferably 1-methyl-2-pyrrolidinone, 1,3-dimethyl-2-imidazolidinone, 2-pyrrolidinone.
  • Amide systems such as ⁇ -caprolactam, formamide, N-methylformamide, N, N-dimethylformamide, acetamide, N-methylacetamide, N, N-dimethylacetamide, N-methylpropanamide, hexamethylphosphoric triamide
  • a solvent can be used.
  • first fluid or the second fluid may contain a dispersing agent such as a block copolymer, a polymer, or a surfactant.
  • a dispersing agent such as a block copolymer, a polymer, or a surfactant.
  • PH adjustment method when the apparatus is used for the pH adjustment method, first, a pigment precipitation solution that changes pH is used as the first fluid from the first introduction part d1 that is one flow path for the rotating process. Introduced between the surfaces 1 and 2, a thin film fluid composed of the first fluid is formed between the processing surfaces.
  • At least one kind of pigment is dissolved in the acidic fluid or alkaline pH adjusting solution or the mixed solution of the pH adjusting solution and the organic solvent as the second fluid from the second introduction part d2 which is another flow path.
  • the pigment solution thus prepared is directly introduced into the thin film fluid composed of the first fluid.
  • the first fluid and the second fluid are disposed between the processing surfaces 1 and 2 whose distance is controlled by the pressure balance between the fluid supply pressure and the pressure applied between the rotating processing surfaces 1 and 2. Can be mixed instantaneously while maintaining the thin film state, and a reaction to form pigment fine particles can be performed.
  • an organic pigment that hardly dissolves in a certain organic solvent is dissolved in an alkaline solution obtained by adding an alkaline substance to the organic solvent to obtain an organic pigment solution (second fluid).
  • an organic pigment solution obtained by adding an alkaline substance to the organic solvent to obtain an organic pigment solution (second fluid).
  • the organic pigment solution By adding the organic pigment solution to water, another organic solvent, an organic solvent not containing the alkaline substance, or a pigment precipitation solution (first fluid) using an acid-containing solvent, the organic pigment solution
  • the reaction in which the pH changes and the pigment precipitates can be performed between the processing surfaces 1 and 2.
  • the acid and alkali to be added may be selected to be added to dissolve or precipitate the pigment depending on the pigment type.
  • the second fluid is introduced from the first introduction part d1 and the first fluid is introduced from the second introduction part d2, contrary to the above. May be introduced.
  • the expressions “first” and “second” in each fluid have only an implication for identification that they are the nth of a plurality of fluids, and a third or higher fluid may exist.
  • the pigment deposition solution that is the first fluid is a solution that can change the pH of the pigment solution, and does not exhibit solubility in the pigment intended for deposition, or is a second fluid.
  • the solubility with respect to a pigment is smaller than the solvent contained in a pigment solution, It consists of water, an organic solvent, or mixtures thereof.
  • the water is preferably purified water such as ion exchange water, pure water, or distilled water.
  • the organic solvent is not particularly limited, but is a monohydric alcohol solvent represented by methanol, ethanol, isopropanol, t-butanol, ethylene glycol, propylene glycol, diethylene glycol, polyethylene glycol, thiodiglycol, dithiodiglycol, 2 Polyhydric alcohol solvents such as methyl-1,3-propanediol, 1,2,6-hexanetriol, acetylene glycol derivatives, glycerin or trimethylolpropane, 1-methyl-2-pyrrolidinone, 1, 3-dimethyl-2-imidazolidinone, 2-pyrrolidinone, ⁇ -caprolactam, formamide, N-methylformamide, N, N-dimethylformamide, acetamide, N-methylacetamide, N, N-dimethylacetamide Amide solvents such as N-methylpropanamide, hexamethylphosphoric triamide, urea, tetramethylurea, etc., ethylene glyco
  • an acidic or alkaline pH adjusting solution obtained by adding an acid or alkaline pH adjusting substance to a solvent.
  • the pH adjusting substance is not particularly limited.
  • an inorganic base such as lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, or barium hydroxide, or a trialkylamine, diazabicyclo is used.
  • Organic alkali such as undecene and metal alkoxide.
  • an acid it is an inorganic acid such as formic acid, nitric acid, sulfuric acid, hydrochloric acid, or phosphoric acid, or an organic acid such as acetic acid, trifluoroacetic acid, oxalic acid, methanesulfonic acid, or trifluoromethanesulfonic acid. They may be added in a solid state, or may be carried out by adding them as an aqueous solution or an organic solvent solution.
  • an inorganic acid such as formic acid, nitric acid, sulfuric acid, hydrochloric acid, or phosphoric acid
  • an organic acid such as acetic acid, trifluoroacetic acid, oxalic acid, methanesulfonic acid, or trifluoromethanesulfonic acid. They may be added in a solid state, or may be carried out by adding them as an aqueous solution or an organic solvent solution.
  • the same solvent as the first fluid can be used. However, it is preferable to select a solvent having higher solubility in the pigment than the solvent contained in the first fluid. Further, the same substance as the first fluid can be added as the pH adjusting substance. It is preferable to select the pH adjusting substance so that the second fluid is more soluble in the pigment than the solvent contained in the first fluid.
  • the mixed solution of the solvent and pH adjusting substance (pH adjusting solution) contained in the first fluid and the second fluid is in a suspended state even in a solution state in which all substances are completely dissolved. Can also be used.
  • an organic solvent may be mixed with the first fluid or the second fluid for the purpose of controlling the crystal type of the pigment or controlling the quality of the pigment.
  • organic solvents can be used.
  • a dispersing agent such as a polymer, a block copolymer, a surfactant, and the like may be included.
  • the pigment used in each of the above methods is not particularly limited, and examples thereof include known organic pigments such as polycyclic quinone pigments, perylene pigments, azo pigments, indigo pigments, quinacridone pigments, and phthalocyanine pigments.
  • pigments include particulate solids and pigments such as dye compounds.
  • examples of the pigment include inorganic achromatic pigments, organic and inorganic chromatic pigments, and colorless or light color pigments, metallic luster pigments, and the like may be used.
  • a newly synthesized pigment may be used. Specific examples of the pigment are given below.
  • black pigments include the following. Raven 1060 10, Raven 1080, Raven 1170, Raven 1200, Raven 1250, Raven 1255, Raven 1500, Raven 2000, Raven 3500, Raven 5250, Raven 5250, Raven 5250 R Company-made). Also, Black PearlsL, Mogu -L, Regal 400R, Regal 660R, Regal 330R, Monarch 800, Monarch 880, Monarch 900, Monarch 1000, Monarch 1300, Monarch 1400, manufactured by Monarch Further, Color Black FW1, Color Black FW2, Color Black FW200, Color Black 18, Color Black S160, Color Black S170, Special Black 4, Special Black 4A, Special Black 6, Printex 35, Printex U, Printex 140U, Printex V, Printex 140V (manufactured by Degussa).
  • Examples of cyan pigments include the following. That is, C. I. Pigment Blue -1, C. I. Pigment Blue -2, C. I. Pigment Blue -3. In addition, C. I. Pigment Blue -15, C. I. Pigment Blue -15: 2, C. I. Pigment Blue -15: 3, C.I. I. Pigment Blue -15: 4. In addition, C. I. Pigment Blue -16, C. I. Pigment Blue -22, C. I. Pigment Blue -60 and the like.
  • magenta pigments examples include the following. That is, C. I. Pigment Red -5, C. I. Pigment Red -7, C. I. PigmentRed -12. In addition, C. I. Pigment Red -48, C. I. Pigment Red -48: 1, C. I. Pigment Red -57, C. I. Pigment Red -112. In addition, C. I. Pigment Red -122, C. I. Pigment Red -123, C. I. Pigment Red -146, C. I. Pigment Red -168. In addition, C. I. Pigment Red -184, C. I. Pigment Red -202, C. I. Pigment Red -207.
  • yellow pigments The following can be listed as yellow pigments. That is, C. I. Pigment Yellow -12, C. I. Pigment Yellow -13, C. I. Pigment Yellow -14, C. I. Pigment Yellow -16. In addition, C. I. Pigment Yellow -17, C. I. Pigment Yellow -74, C. I. Pigment Yellow -83, C. I. Pigment Yellow -93. In addition, C. I. Pigment Yellow -95, C. I. Pigment Yellow -97, C. I. Pigment Yellow-98, C. I. Pigment Yellow -114. In addition, C. I. Pigment Yellow -128, C. I. Pigment Yellow -129, C.I. I. Pigment Yellow 151, C. I. Pigment “Yellow-154”.
  • pigments can be used depending on the target color. Typical examples include purple pigments such as Pigment Violet -23, green pigments such as Pigment Green -7, and orange pigments such as Pigment Orange -43. Can be implemented.
  • a dye can be used in the same manner as the pigment.
  • C. I. Solvent Blue C. 33, -38, -42, -45, -53, -65, -67, -70, -104, -114, -115, -135.
  • C. I. Solvent Red C. -25, -31, -86, -92, -97, -118, -132, -160, -186, -187, -219.
  • Water-soluble dyes can also be used.
  • Direct Blue -6, -22, -25, -71, -78, -86, -90, -106, -199; C. I. Direct orange, -34, -39, -44, -46, -60; C. I. Direct violet, -47, -48; C. I. Direct Brown, -109; C. I. Direct green, direct dyes such as -59, C. I. Acid Black, -2, -7, -24, -26, -31, -52, -63, -112, -118, -168, -172, -208; C. I.
  • Acid Yellow -11, -17, -23, -25, -29, -42, -49, -61, -71;
  • Acid Blue -9, -22, -40, -59, -93, -102, -104, -113, -117, -120, -167, -229, -234, -254;
  • C. I. Acid violet, acidic dyes such as ⁇ 49, C. I. Reactive Black, -1, -5, -8, -13, -14, -23, 31-1, -34, -39; C. I.
  • Reactive Yellow -2, -3, -13, -15, -17, -18, -23, -24, -37, -42, -57, -58, -64, -75, -76,- 77, -79, -81, -84, -85, -87, -88, -91, -92, -93, -95, -102, -111, -115, -116, -130, -131, -132, -133, -135, -137, -139, -140, -142, -143, -144, -145, -146, -147, -148, -151, -162, -163; I.
  • Reactive Red Reactive Red, -3mm, -13mm, -16mm, -21mm, -22mm, -23mm, -24mm, -29, -31mm, -33mm, -35mm, -45mm, -49mm, -55mm, -63mm,- 85, -106, -109, -111, -112, -113, -114, -118, -126, -128, -130, -131, -141, -151, -170, -171, -174, -176, -177, -183, -184, -186, -187, -188, -190, -193, -194, -195, -196, -200, -201, -202, -204, -206 , -218, -221; C.
  • Reactive Orange -5, -7, -11, -12, -13, -15, -16, -35, -45, -46, -56, -62, -70, -72, -74,- 82, -84, -87, -91, -92, -93, -95, -97, -99; C.
  • Reactive violet -1, -4, -5, -6, -22, -24, -33, -36, -38;
  • Reactive Green -5, -8, -12, -15, -19, -23; C. I.
  • Reactive dyes such as reactive brown, -2, -7, -8, -9, -11, -16, -17, -18, -21, -24, -26, -31, -32, -33; C. I. Basic Black, -2; C. I. Basic Red, -1, -2, -9, -12, -13, -14, -27; C. I. Basic Blue, -1, -3, -5, -7, -9, -24, -25, -26, -28, -29; C. I. Basic violet, -7, -14, -27; C. I. Food black, -1, -2, etc. are mentioned.
  • Dyes that can be used may be known or new ones.
  • direct dyes, acid dyes, basic dyes, reactive dyes, water-soluble dyes for food coloring, fat-soluble (oil-soluble) dyes, or insoluble dyes of disperse dyes as described below can be used. These may be used in a solid state. In this respect, for example, oil-soluble dyes may be used.
  • the oil-soluble dye refers to a dye that dissolves in an organic solvent, and is also referred to as a fat-soluble dye.
  • the surfactant and dispersant various commercially available products used for pigment dispersion can be used. Although not particularly limited, for example, dodecylbenzene sulfonic acid type such as Neogen RK (Daiichi Kogyo Seiyaku), Solsperse 2000020, Solsperse 24000, Solsperse 26000, Solsperse 27000, Solsperse 28000, Solsperse 41090 (above, manufactured by Abyssia) , Disperbic 160, Disperbic 161 ⁇ , Disperbic 162, Disperbic 163, Disperbic 166, Disperbic 170, Disperbic 180, Disperbic 181, Disperbic 182, Disperbic-183, Disperbic 184, Disperbic 190, Dispersic 191, Dispersic 192, Dispersic-2000, Disper -2001 (above, manufactured by BYK Chemie), Polymer 1 ⁇ ⁇ ⁇ ⁇ 00, Polymer 120, Polymer 150, Polymer 400,
  • block copolymer examples include the following. That is, acrylic, methacrylic block copolymers, polystyrene and other addition polymerization or condensation polymerization block copolymers, block copolymers having polyoxyethylene and polyoxyalkylene blocks, and the like.
  • a conventionally known block copolymer can also be used.
  • the block copolymer used in the present invention is preferably amphiphilic. As a particularly preferred form, there can be mentioned a diblock copolymer comprising a hydrophobic segment and a hydrophilic segment having an organic acid or an ionic salt unit thereof.
  • a triblock copolymer having a hydrophobic segment, a hydrophilic segment having an organic acid or an ionic salt unit thereof, and another segment is preferably used.
  • a form that is a hydrophobic segment, a nonionic hydrophilic segment, a hydrophilic segment having an organic acid or an ionic salt unit thereof is preferably used, and is also preferable in terms of stabilization of the inclusion state.
  • the pigment when the above-described triblock copolymer is used to prepare a dispersion using a pigment substance and water as a solvent, the pigment can be encapsulated in micelles formed by the triblock copolymer. Thus, it is possible to form a pigment-encapsulated ink composition.
  • the particle size of the particles of the dispersion composition can also be made very uniform and uniform. Furthermore, the dispersion state can be made extremely stable. When these treatments are carried out using the above apparatus, the particle diameters of the pigment fine particles are very uniform and the uniformity is further improved.
  • a pigment may be directly synthesized in a thin film fluid.
  • a copper phthalocyanine pigment is obtained by reacting phthalic anhydride or a derivative thereof, copper or a compound thereof, urea or a derivative thereof and a catalyst in an organic solvent or in the absence thereof.
  • Pigments may be directly synthesized using various reactions, as represented by the method.
  • a process for pulverizing coarse pigment fine particles produced by the synthesis process is necessary. A shearing force can be applied therein, and a grinding step can be included.
  • mixing in the mixing channel can be performed under laminar flow control or turbulent flow control.
  • UV ultraviolet rays
  • a jacket through which a heater, a heat medium, and a refrigerant are passed is provided in at least one or both of the processing units 10 and 20, so that the thin film fluid can be heated and cooled.
  • the processing fluid is heated and the reaction is accelerated by providing a microwave generator such as a magnetron for irradiating at least one or both of the processing units 10 and 20 with microwaves.
  • a microwave generator such as a magnetron for irradiating at least one or both of the processing units 10 and 20 with microwaves.
  • an element such as a lamp for irradiating ultraviolet rays is provided on at least one or both of the processing units 10 and 20, and ultraviolet rays (UV) are applied to the thin film fluid from the corresponding processing surfaces.
  • At least one or both of the processing units 10 and 20 can be provided with an ultrasonic oscillator, and mixing and reaction between the processing surfaces can be performed in an ultrasonic atmosphere. It can also be carried out in a container.
  • the deposition is performed in a container capable of securing a reduced pressure or a vacuum state, and at least the secondary side from which the fluid is discharged after the processing is set to a reduced pressure or a vacuum state, whereby the gas generated during the precipitation reaction and the fluid are contained in the fluid.
  • the contained gas can be degassed or the fluid can be desolvated.
  • a third introduction part d3 can be provided in the processing apparatus as described above.
  • a solution containing water or an organic solvent a fluid containing an acid in which the pigment is dissolved, an organic solvent for the purpose of controlling the crystal form of the pigment and controlling the quality of the pigment, etc. are separately introduced into the processing apparatus.
  • a pigment precipitation solution for changing the pH, a fluid containing the pigment solution, an organic solvent for the purpose of controlling the crystal form of the pigment and controlling the quality of the pigment, etc. Etc. can be separately introduced into the processing apparatus.
  • concentration and pressure of each solution can be managed separately, and the reaction which pigment fine particles produce
  • the fourth or more introduction portions are provided, and the fluid to be introduced into the processing apparatus can be subdivided in this way.
  • the apparatus used in the present invention can freely change the Reynolds number of the thin film fluid, the fine particles of the pigment are monodispersed and have good redispersibility according to the purpose, such as particle diameter, particle shape, crystal type, etc. Can be made. Moreover, due to its self-discharging properties, there is no clogging of the product even in the case of a reaction involving precipitation, and a large pressure is not required. Therefore, pigment fine particles can be stably produced, and are excellent in safety, hardly contaminated with impurities, and have good cleaning properties. Furthermore, since it can be scaled up according to the target production volume, it is possible to provide a method for producing pigment fine particles with high productivity.
  • the following precipitation reaction of biologically ingested particulates is arranged so as to be able to approach and separate from each other, and at least one of them is uniformly mixed between the processing surfaces 1 and 2 rotating with respect to the other. Occur. Control of the particle size, monodispersity, or crystal type of fine particles in the body intake is controlled by the rotational speed of the processing surfaces 1 and 2, the distance between the processing surfaces 1 and 2, and the flow velocity, temperature, or raw material concentration of the thin film fluid. It can be adjusted by changing etc. This point is as pointed out by the present applicant in Patent 4419157, etc., and the present applicant emphasizes the precipitation step and adjusts the rotation speed, flow rate, and distance between the processing surfaces.
  • the ingestible particulate raw material is mixed with a solvent that can be a second solvent having a lower solubility than the first solvent to precipitate the ingested particulate matter.
  • the aforementioned biological intake contains a drug.
  • the invention can be practiced with a wide variety of drugs.
  • the drug is preferably an organic substance that exists in a substantially pure state.
  • the drug must be dispersible with low solubility in at least one solvent and must be soluble in at least one solvent.
  • Low solubility means that the drug has a solubility of less than about 10 mg / mL, preferably less than about 1 mg / mL in a solvent (eg, water) at the processing temperature (eg, room temperature).
  • soluble means to dissolve at 10 mg / mL or more.
  • a dispersant surfactant
  • a water-soluble polymer e.g., ethylene glycol dimethacrylate
  • a stabilizer e.g., ethylene glycol dimethacrylate
  • a preservative e.g., sodium bicarbonate
  • a pH adjuster e.g., sodium bicarbonate
  • an isotonic agent e.g., sodium bicarbonate
  • Suitable drugs include, for example, analgesics, anti-inflammatory drugs, anthelmintic drugs, antiarrhythmic drugs, antibiotics (including penicillins), anticoagulants, antihypertensive drugs, antidiabetic drugs, antiepileptic drugs, antihistamines, Antineoplastic, anti-obesity, appetite suppressant, antihypertensive, antimuscarinic, antimycobacterial, antineoplastic, immunosuppressive, antithyroid, antibacterial, antiviral, anxiolytic (hypnotic Drugs and neuroleptics), astrinsents, adrenergic beta-receptor blockers, blood products and plasma substitutes, myocardial degenerative drugs, contrast media, corticosteroids, cough suppressants (descendants and mucus destroyers), diagnostic agents, Diagnostic imaging agents, diuretics, dopamine agonists (anti-Parkinson's disease drugs), hemostatic agents, immune agents, lipid modulators, muscle relaxants, parasympathomim
  • Preferred drugs include those intended for oral administration and injection with low solubility in water.
  • a description of these classes of drugs and the list contained in each class can be found in “Martindale, The Extra Pharmacopoeia, 29th edition, The h Pharmaceutical Press, London, 1989”. These drugs are commercially available or can be prepared by methods known in the art.
  • drugs useful in the practice of this invention include 17- ⁇ -pregno-2,4-diene-20-ino- [2,3-d] -isoxazol-17-ol (danazol), tacrolimus Hydrate, progesterone, tranilast, benzbromarone, mefenamic acid, [6-methoxy-4- (1-methylethyl) -3-oxo-1,2-benzisothiazol-2 (3H) -yl] methyl 2 , 6-dichlorobenzoate 1,1-dioxide (WIN 63,394), 3-amino-1,2,4-benzotriazine-1,4-dioxide (WIN 59,075), piperosulfam, piperosulphane, camptothecin, Acetominophen, acetylsalicylic acid, amiodarone, colestifmine, colestipol, cromolyn sodium, alb Roll, sucralfate, sulfasalazine
  • the drug is an immunosuppressant such as Danazol or tacrolimus hydrate, an antiallergic agent such as tranilast, a steroid such as progesterone, an antiviral agent, an antineoplastic agent or anti-inflammatory. It is a medicine.
  • Particularly preferred stabilizers / dispersants include sodium dodecylbenzenesulfonate, sodium dodecyl sulfate, sodium tetradecyl sulfate, sodium pentadecyl sulfate, sodium octyl sulfate, sodium oleate, sodium laurate, sodium stearate, Calcium stearate, Tween 20 and Tween 80 (these are polyoxyethylene sorbitan fatty acid esters available from ICI Specialty Chemicals), polyvinyl pyrrolidone, tyloxapol, Pluronic F68 and F108 (which are ethylene oxide available from BASF) A block copolymer of propylene oxide), Tetronic 908 (T908) (which is a tetrafunctional block copolymer derived from the continuous addition of ethylene oxide and propylene oxide to ethylenediamine, available from BASF), dextran, lecithin, Aerosol OT
  • water-soluble polymer examples include methyl cellulose, ethyl cellulose, propyl methyl cellulose, propyl cellulose, carboxymethyl cellulose, polyvinyl alcohol, and polyvinyl pyrrolidone.
  • the content of the drug in the present invention is not particularly limited. It is also possible to prepare a suspension with a high concentration and dilute it according to the concentration to be used.
  • the stabilizer examples include sodium edetate, sodium sulfite, sodium hydrogen sulfite, sodium thiosulfate, dibutylhydroxytoluene, tocopherol and the like.
  • preservative examples include paraoxybenzoic acid ester, chlorobutanol, phenylethyl alcohol, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, alkylpolyaminoethylglycines, and sorbic acid.
  • pH adjusters examples include hydrochloric acid, sulfuric acid, acetic acid, lactic acid, citric acid, tartaric acid, malic acid, phosphoric acid, boric acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, monoethanolamine, diethanolamine, diethylamine, ammonia and These salts can be mentioned.
  • isotonic agents examples include sodium chloride, potassium chloride, calcium chloride, mannitol and the like.
  • water such as ultrapure water or ion exchange water, and methyl alcohol, ethyl alcohol, acetone, dimethylformamide, dimethylacetamide depending on the purpose.
  • a water-miscible organic solvent such as dimethyl sulfoxide and a water-immiscible organic solvent such as octane, cyclohexane, benzene, xylene, diethyl ether, and ethyl acetate can be appropriately selected according to the purpose.
  • the biologically ingestible particulate of the present invention is not particularly limited as long as it is intended to be ingested by the living body, but for example, it is absorbed into the living body like a drug in a pharmaceutical product and exhibits an in vivo effect.
  • Those intended to be applied those that pass through the body, such as barium sulfate as a contrast agent, those that are applied to living skin, such as substances for transporting drug components in drug delivery systems, or cosmetics, and Examples include foods and intermediates of the above substances.
  • the precipitation reaction of the fine particles is performed while forcibly and uniformly mixing between the processing surfaces 1 and 2 which are disposed so as to be able to approach and separate from each other in the apparatus shown in FIG. Occur.
  • the solution containing the first solvent is disposed to face each other so as to be able to approach and leave, and at least one of the processing surfaces rotates with respect to the other.
  • a thin film fluid composed of a first fluid is created between the processing surfaces.
  • a solvent that can be a second solvent having a lower solubility than the first solvent is directly introduced into the thin film fluid composed of the first fluid from the second introduction part d2 that is a separate flow path.
  • the solution containing the first solvent and the second solvent are disposed between the processing surfaces 1 and 2 whose distance is fixed by the pressure balance between the fluid supply pressure and the pressure applied between the rotating processing surfaces. Can be mixed to perform precipitation reaction of fine particles.
  • the second solvent is introduced from the first introduction part d 1 and the first solvent is introduced from the second introduction part d 2. It is also possible to introduce a solution containing.
  • the expressions “first” and “second” in each solvent only have a meaning for identification that they are the n-th of a plurality of solvents, and third or more solvents may exist.
  • a third introduction part d3 can be provided in the processing apparatus.
  • the first solvent is introduced from each introduction part.
  • the solution containing the solution, the second solvent, and the solution containing the stabilizer / dispersant can be separately introduced into the processing apparatus. If it does so, the density
  • the fourth or more introduction portions are provided, and the fluid to be introduced into the processing apparatus can be subdivided in this way.
  • “from the center” means “from the first introduction part d1” of the processing apparatus shown in FIG. 1, and the first fluid is introduced from the first introduction part d1.
  • the first fluid to be treated refers to the second fluid to be treated, which is introduced from the second introduction part d2 of the treatment apparatus shown in FIG.
  • the opening d20 of the second introduction part d2 a concentric annular shape surrounding the central opening of the processing surface 2 was used as shown by a dotted line in FIG.
  • the primary particle diameter was observed for a plurality of visual fields using JEM-2100 manufactured by JEOL.
  • the observation magnification was 50,000 times or more, and the average value of the primary particle diameters of 100 fine particles confirmed by TEM observation was adopted as the average particle diameter.
  • the observation magnification was 30,000 times or more, and the average value of the primary particle diameters of 100 fine particles confirmed by TEM observation was adopted as the average particle diameter.
  • X-ray diffraction (XRD) measurement a powder X-ray diffraction measurement apparatus X'Pert PRO MPD (manufactured by XRD Spectris PANalytical Division) was used.
  • the measurement conditions are Cu counter cathode, tube voltage 45 kV, tube current 40 mA, 0.016 step / 10 sec, and the measurement range is 10 to 60 [° 2 Theta] (Cu).
  • the degree of crystallinity of the obtained fine particles and the composition ratio of the specific crystal type were calculated from the XRD measurement results.
  • the crystallinity was calculated by the constant background method from the XRD measurement results obtained in each experiment, assuming that the crystallinity of the pigment bulk powder was 100%.
  • the composition ratio of the specific crystal type that is a ⁇ -type crystal (hereinafter referred to as ⁇ -type crystal ratio) is determined from the measurement results, the peak intensity I ⁇ near 27.5 ° that appears as a characteristic peak in the ⁇ -type crystal, and the ⁇ -type crystal.
  • ⁇ -type crystal ratio (I ⁇ / (I ⁇ + I ⁇ )) ⁇ 100 [%] (4)
  • the measurement conditions are Cu counter cathode, tube voltage 45 kV, tube current 40 mA, 0.016 step / 10 sec, and the measurement range is 10 to 45 [° 2 Theta] (Cu).
  • the degree of crystallinity of the obtained fine particles and the composition ratio of the specific crystal type were calculated from the XRD measurement results.
  • the crystallinity was calculated by the constant background method from the XRD measurement results obtained in each experiment, assuming that the crystallinity of the bulk powder was 100%.
  • the composition ratio of the specific crystal type that is the ⁇ -type crystal (hereinafter referred to as the ⁇ -type crystal ratio) is determined from the measurement result, the peak intensity I ⁇ near 29.5 ° that appears as a characteristic peak in the ⁇ -type crystal, and the ⁇ -type crystal.
  • Example 3 (Preparation of PR122 fine particles using acid pasting method) (Examples 1 to 3) Using the fluid processing apparatus shown in FIG. 1, at least one of the pigment solution, which is a fine particle raw material solution, and a deposition solvent are disposed opposite to each other and have a processing surface that can be approached and separated, with respect to the other. Then, the mixture was mixed in a thin film fluid formed between the processing surfaces 1 and 2 rotating, and pigment fine particles were precipitated in the thin film fluid.
  • the pigment solution is prepared using a stirrer having a rotating stirring blade, and at least one of the three conditions (stirring time, stirring blade peripheral speed, and temperature of the fine particle raw material solution) defining the stirring energy is changed. The stirring energy was increased or decreased. In Examples 1 to 3, the stirring energy was increased or decreased by changing the temperature (preparation temperature) of the pigment solution.
  • a pigment solution was prepared using a stirrer (CLEAMIX (manufactured by M Technique Co., Ltd.)) having rotating stirring blades as shown in FIGS.
  • CLEAMIX manufactured by M Technique Co., Ltd.
  • PR122 was added to 10 wt% fuming sulfuric acid so that the total amount would be 3 wt%, and the pigment was prepared in the nitrogen atmosphere at the preparation time, preparation temperature, and peripheral speed of the stirring blade in Table 2.
  • the solution was stirred and 3 wt% PR122 was dissolved in 10 wt% fuming sulfuric acid.
  • the pigment solution is treated as the second fluid while feeding methanol (MeOH) from the center as methanol (MeOH) at a supply pressure / back pressure of 0.121 MPaG / 0.020 MPaG and a rotational speed of 2500 rpm.
  • the first fluid and the second fluid were mixed in the thin film fluid by introducing between the working surfaces.
  • PR122 fine particle dispersion was discharged from between the processing surfaces 1 and 2.
  • the PR122 fine particle dispersion was loosely agglomerated, and as a washing operation, the PR122 fine particle dispersion was precipitated by a centrifuge ( ⁇ 18000G), and the supernatant was removed.
  • the ratio to the average particle size (hereinafter, the crystallinity of PR122 fine particles / average particle size and the ⁇ -type crystal ratio of PR122 fine particles / average particle size) was evaluated. did. This is because the scattering intensity in the XRD measurement varies depending on the particle diameter of the PR122 fine particles to be measured by XRD, and normalization is performed by dividing by the particle diameter. In the present invention, when the numerical change is observed by dividing by the average particle diameter as described above, it is suitable when the width of the change in the particle diameter is in the nano-order range of 3 digits, and within the 2-digit range.
  • Table 1 shows the processing conditions (prescription and operating conditions) of the first fluid and the second fluid.
  • Table 2 shows the conditions for preparing the second fluid and the results obtained.
  • the target temperatures of the first fluid and the second fluid shown in Table 1 are set temperatures of the temperature controller (heating / cooling) when each of the first fluid and the second fluid is introduced into the processing apparatus.
  • FIG. 6 shows changes in crystallinity / average particle diameter and ⁇ -type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation temperature of the second fluid in Examples 1 to 3. From FIG. 6, it can be seen that when the preparation temperature of the second fluid increases, the numerical values of the degree of crystallinity / average particle diameter and ⁇ -type crystal ratio / average particle diameter of the obtained PR122 fine particles increase. Further, from Table 2, it is recognized that the average particle diameter of the obtained PR122 fine particles decreases as the preparation temperature of the second fluid increases.
  • Examples 4 to 16 A dry powder of PR122 fine particles was obtained in the same manner as in Examples 1 to 3 except that the preparation conditions of the pigment solution were changed to any of Tables 3 to 5. The results are shown in Tables 3-5. In Examples 4 to 16, the stirring energy was increased or decreased by changing the stirring time (preparation time) of the pigment solution as the second fluid.
  • Examples 4 to 7 changes in the degree of crystallinity / average particle diameter and ⁇ -type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid are shown in FIG. Changes in crystallinity / average particle diameter and ⁇ -type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation time of two fluids are shown in FIG. Changes in crystallinity / average particle size and ⁇ -type crystal ratio / average particle size are shown in FIG. In Examples 8 to 11 and Examples 12, 13, 15, and 16, the change in crystallinity / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid is shown in FIG. FIG.
  • Example 17 to 22 A dry powder of PR122 fine particles was obtained in the same manner as in Examples 1 to 3 except that the preparation conditions of the pigment solution were changed to Table 6 or 7. The results are shown in Tables 6-7.
  • the stirring energy was increased or decreased by changing the peripheral speed of the stirring blade when preparing the pigment solution as the second fluid.
  • Example 17 to 22 the change in crystallinity / average particle diameter of PR122 fine particles with respect to the peripheral speed of the stirring blade at the time of preparing the second fluid is shown in FIG. 12, and in Examples 17 to 22 at the time of preparing the second fluid FIG. 13 shows changes in the ⁇ -type crystal ratio / average particle diameter of PR122 fine particles with respect to the peripheral speed of the stirring blade. 12 to 13, when the peripheral speed of the stirring blade at the time of preparing the second fluid increases, the numerical values of crystallinity / average particle diameter, ⁇ -type crystal ratio / average particle diameter of the obtained PR122 fine particles tend to increase. The same tendency was recognized also in the Example which changed the preparation time of the 2nd fluid in addition to the change of the said peripheral velocity. Further, from Tables 6 to 7, it is recognized that the average particle diameter of the obtained PR122 fine particles decreases as the peripheral speed of the stirring blade during the second fluid preparation increases.
  • the present invention can derive the following matters regarding the setting of the priority of the preparation conditions of the second fluid in order to increase or decrease the stirring energy from the results of the above-described embodiment. From the results of Examples 1 to 3, when the second fluid was prepared with the preparation temperature maintained at 60 ° C. (Example 3), the stirring time spent for preparation was as short as 30 minutes, and the stirring blade of the stirrer The peripheral speed is a relatively low speed of 18.85 m / sec.
  • Example 13 to 16 in comparison with the other cases (Examples 13 to 16) in which the temperature during preparation in which a longer stirring time was consumed and the peripheral speed was maintained at a higher speed than in this case was relatively low (Examples 13 to 16), Can obtain fine particles having a small average particle diameter with respect to the obtained PR122, and the influence of the preparation temperature on the properties / characteristics of the fine particles is the strongest.
  • Example 16 where the stirring time was sufficiently long as 180 minutes, it finally became the same as the result of Example 3, and it was possible to obtain fine particles having a small average particle diameter with respect to the obtained PR122.
  • Example 3 when the preparation temperature of the second fluid is relatively low, even if the peripheral speed is kept higher and a longer stirring time is spent, The average particle diameter of the obtained PR122 fine particles is not as small as Example 3. That is, as in Example 3, if the preparation temperature of the second fluid is kept slightly higher, fine particles having a small average particle diameter can be obtained even if the stirring time is shortened and the peripheral speed is kept low. Become.
  • Example 19 and Example 22 in which the peripheral speed was 31.42 m / sec were obtained in comparison with the above-described examples in which the peripheral speed was 18.85 m / sec and 25.13 m / sec.
  • the average particle size of the obtained PR122 fine particles does not reach the results of Examples 1 to 3 and Examples 4 to 16.
  • the same relationship is also obtained for the relationship between the above description, the degree of crystallinity, and the ⁇ -type crystal ratio. This is because, when the crystallinity and ⁇ -type crystal ratio are not divided by the average particle size, it was difficult to show a clear numerical change, but crystallinity / average particle size, ⁇ -type crystal ratio / average particle size.
  • the particle size of fine particles, the color and coloring power, and the “crystallinity”, which is an index for evaluating durability, and the “ ⁇ -type crystal ratio” naturally differ depending on the use of the fine particles. What is necessary is just to perform control according to the use of fine particles. Further, in the present invention, when the numerical change is observed by dividing by the average particle diameter as described above, it is suitable when the width of the change in the particle diameter is in the range of 3 digits in the nano order, and in the range of 2 digits. It is more preferable to stop at
  • the pigment solution is prepared using a stirrer having a rotating stirring blade, and the temperature of the pigment solution (the stirring time, the peripheral speed of the stirring blade, and the temperature of the fine particle raw material solution) among the three conditions that define the stirring energy (The stirring energy was increased or decreased by changing the preparation temperature) and / or the stirring time (preparation time).
  • Two fluids were introduced between the processing surfaces, and the first fluid and the second fluid were mixed in the thin film fluid.
  • PR122 fine particle dispersion was discharged from between the processing surfaces 1 and 2.
  • the PR122 fine particle dispersion was loosely agglomerated, and as a washing operation, the PR122 fine particle dispersion was precipitated by a centrifuge ( ⁇ 18000G), and the supernatant was removed. Thereafter, pure water was added to re-disperse the PR122 fine particle dispersion, and the precipitate was precipitated again using a centrifuge. After performing the washing operation three times, the finally obtained PR122 fine particle dispersion paste was vacuum dried at 50 ° C. and ⁇ 0.1 MPaG to obtain a dry powder of PR122 fine particles.
  • the obtained dry powder of PR122 fine particles was subjected to TEM observation and XRD measurement, and the particle diameter, crystallinity, and ⁇ -type crystal ratio were determined.
  • the values of the crystallinity and ⁇ -type crystal ratio are the ratios to the average particle diameter (hereinafter referred to as the crystallinity of PR122 fine particles / average particle diameter and the ⁇ -type crystals of PR122 fine particles as in Examples 1 to 22). (Ratio / average particle size).
  • Tables 8 to 10 show the processing conditions (formulation and operating conditions) for the first fluid and the second fluid, the preparation conditions for the second fluid, and the results obtained.
  • the temperatures (target temperatures) of the first fluid and the second fluid shown in Table 8 are set temperatures of the temperature controller (heating / cooling) when each of the first fluid and the second fluid is introduced into the processing apparatus.
  • the temperatures of the first fluid and the second fluid shown in Table 9 or 10 are just before introducing each of the first fluid and the second fluid into the processing apparatus (more specifically, introduced between the processing surfaces 1 and 2). The temperature measured immediately before).
  • Examples 23 to 31 the change in crystallinity / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid is shown in FIG. 14, and in Examples 23 to 31, the change in PR122 fine particles with respect to the preparation time of the second fluid is shown in FIG.
  • the change in ⁇ -type crystal ratio / average particle diameter is shown in FIG. 15 and in Examples 23 to 31, the change in crystallinity / average particle diameter of PR122 fine particles with respect to the preparation temperature of the second fluid is shown in FIG.
  • FIG. 17 shows changes in ⁇ -type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation temperature of the second fluid at ⁇ 31.
  • Examples 32 to 40 the change in crystallinity / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid is shown in FIG. 18, and in Examples 32 to 40, PR122 with respect to the preparation time of the second fluid. Changes in ⁇ -type crystal ratio / average particle size of fine particles are shown in FIG. 19, and changes in crystallinity / average particle size of PR122 fine particles with respect to the preparation temperature of the second fluid in Examples 32 to 40 are shown in FIG. In Examples 32 to 40, changes in ⁇ -type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation temperature of the second fluid are shown in FIG. As shown in FIGS. 14 to 15 and FIGS.
  • the ⁇ -type crystal ratio was determined for the obtained PR122 fine particles, and the ⁇ -type crystal ratio / average particle diameter was evaluated.
  • the composition ratio of the specific crystal type that is an ⁇ -type crystal ( ⁇ -type crystal ratio) ) And the ⁇ -type crystal ratio / average particle diameter may be evaluated.
  • it fluctuates by changing at least one of the three conditions (stirring time, stirring blade peripheral speed, temperature of the fine particle raw material solution) that regulate the stirring energy, and increasing or decreasing the stirring energy.
  • the variation rate of the average particle diameter tends to be larger than the variation rate of the ⁇ -type crystal ratio and ⁇ -type crystal ratio, and either ⁇ -type crystal ratio / average particle diameter or ⁇ -type crystal ratio / average particle diameter is evaluated. However, it is for showing the same tendency.
  • Example 17 by changing the peripheral speed of the stirring blade at the time of preparing the pigment solution as the second fluid, the peripheral speed condition satisfying the specific condition for the average particle diameter of the obtained PR122 fine particles is decide.
  • the specific condition is Example 17 in which the average particle diameter of PR122 fine particles is the largest, and the peripheral speed of 18.85 m / sec is determined as the peripheral speed condition.
  • the PR122 fine particle crystals A stirring time condition and a temperature condition satisfying specific conditions for the degree of conversion and the crystal form are determined.
  • Example 4 having a high “crystallinity” and a high “ ⁇ -type crystal ratio” was determined as a specific condition, and its preparation time (stirring time) of 30 minutes was determined as a stirring time condition. To do. Further, in Examples 1 to 3 and 4 (Example 17) of the present application, Example 4 (Example 17) having a high “crystallinity” and a high “ ⁇ -type crystal ratio” is set as a specific condition, and the temperature is set. 28 ° C. (preparation temperature) is determined as a temperature condition. And it can implement as what manufactures the microparticles
  • the setting of the specific condition is merely an example, and is not limited to the above example.
  • an indomethacin solution which is a fine particle raw material solution, and a precipitation solvent are disposed so as to face each other and have an approachable / separable treatment surface, at least one of which is opposite to the other Were mixed in a thin film fluid formed between the rotating processing surfaces 1 and 2 to precipitate indomethacin fine particles in the thin film fluid.
  • the indomethacin solution is prepared using a stirrer having a rotating stirring blade, and the temperature of the indomethacin solution (the stirring time, the peripheral speed of the stirring blade, and the temperature of the fine particle raw material solution) among the three conditions that regulate the stirring energy (The stirring energy was increased or decreased by changing the preparation temperature) and / or the stirring time (preparation time).
  • an indomethacin solution was prepared using a stirrer (CLEAMIX (manufactured by M Technique Co., Ltd.)) having a rotating stirring blade shown in FIGS. Specifically, using Claremix, indomethacin was added while stirring diethyl ether at the peripheral speed of the stirring blade of Table 12, and the indomethacin solution was stirred at the preparation time and preparation temperature shown in Table 12, and 1.5 wt. A% indomethacin solution was prepared.
  • CLEAMIX manufactured by M Technique Co., Ltd.
  • the indomethacin solution is used as the second fluid between the processing surfaces.
  • the first fluid and the second fluid were mixed in the thin film fluid.
  • the indomethacin fine particle dispersion was discharged from between the processing surfaces 1 and 2.
  • the indomethacin fine particle dispersion was loosely aggregated, and the indomethacin fine particle dispersion was settled with a centrifuge ( ⁇ 8000 G) as a washing operation, and the supernatant was removed. Thereafter, pure water was added to re-disperse the indomethacin fine particle dispersion, and the precipitate was precipitated again using a centrifuge. After performing the washing operation three times, the finally obtained paste of indomethacin fine particle dispersion was vacuum-dried at 25 ° C. and ⁇ 0.1 MPaG to obtain a dry powder of indomethacin fine particles.
  • crystallinity and ⁇ -type crystal ratio are the ratios to the average particle size (hereinafter referred to as crystallinity / average particle size of indomethacin fine particles and ⁇ -type crystals of indomethacin fine particles as in Examples 1 to 40). (Ratio / average particle size).
  • Tables 11 to 12 show the processing conditions (prescription and operating conditions) of the first fluid and the second fluid, the preparation conditions of the second fluid, and the obtained results.
  • the temperatures (target temperatures) of the first fluid and the second fluid shown in Table 11 are set temperatures of the temperature controller (heating / cooling) when each of the first fluid and the second fluid is introduced into the processing apparatus.
  • the temperatures of the first fluid and the second fluid shown in Table 12 are just before introducing each of the first fluid and the second fluid into the processing apparatus (more specifically, immediately before introducing between the processing surfaces 1 and 2). The measured temperature.
  • Example 41 to 49 the change in crystallinity / average particle diameter of indomethacin fine particles with respect to the preparation time of the second fluid is shown in FIG.
  • the change in crystallinity / average particle diameter is shown in FIG.
  • the change in ⁇ -type crystal ratio / average particle size of indomethacin fine particles with respect to the preparation time of the second fluid is shown in FIG.
  • FIG. 25 shows the change in ⁇ -type crystal ratio / average particle diameter of indomethacin fine particles.
  • the preparation temperature was 33 ° C., 25 ° C., or 5 ° C.
  • the average particle size of the indomethacin fine particles obtained decreases, and both the crystallinity / average particle size and the ⁇ -type crystal ratio / average particle size tend to increase.
  • the preparation time was 15 minutes, 30 minutes.
  • the average particle diameter of the indomethacin fine particles obtained increases as the preparation temperature rises, and both the crystallinity / average particle diameter and the ⁇ -type crystal ratio / average particle diameter tend to decrease. Appears.
  • the preparation time of the second fluid is short (when the preparation time is 15 minutes)
  • the crystallinity of the indomethacin microparticles obtained regardless of the preparation temperature of the second fluid It can be seen that there is almost no difference between / average particle size and ⁇ -type crystal ratio / average particle size.
  • the preparation time of the second fluid is 60 minutes
  • the difference in crystallinity / average particle diameter and ⁇ -type crystal ratio / average particle diameter of the indomethacin fine particles obtained is very large depending on the preparation temperature.
  • the preparation time of the second fluid is 30 minutes, although the difference in crystallinity / average particle diameter and ⁇ -type crystal ratio / average particle diameter of the indomethacin fine particles obtained depends on the preparation temperature, The difference is reduced compared to the case where the preparation time of the second fluid is 60 minutes. That is, referring to FIG. 22 and FIG.
  • the degree of crystallinity of the indomethacin fine particles / average particle size change and the amount of change in the ⁇ -type crystal ratio / average particle size with respect to the preparation time of the second fluid are as follows.
  • An example of the control method in this case is as follows. First, the preparation temperature of the second fluid is set high, and then the preparation time of the second fluid is set to thereby change the desired crystallinity / average particle diameter and ⁇ type. The crystal ratio / average particle diameter can be easily obtained. Further, in order to increase the crystallinity / average particle diameter and ⁇ -type crystal ratio / average particle diameter with the same preparation time of the second fluid, the preparation temperature may be set low, and the preparation time of the second fluid is the same.
  • the preparation temperature may be set high. Referring to FIGS. 23 and 25, by maintaining the preparation temperature of the second fluid at 33 ° C., which is slightly higher than room temperature, the crystallinity / degree of the indomethacin fine particles obtained can be obtained regardless of the preparation time of the second fluid. It can be seen that there is almost no difference between the average particle diameter and the ⁇ -type crystal ratio / average particle diameter. When the preparation temperature of the second fluid is 5 ° C., the difference in crystallinity / average particle diameter and ⁇ -type crystal ratio / average particle diameter of the indomethacin fine particles obtained is very large depending on the length of the preparation time.
  • the difference in crystallinity / average particle diameter and ⁇ -type crystal ratio / average particle diameter of the indomethacin fine particles obtained depends on the length of the preparation time. Although it occurs, the difference is reduced compared to the case where the preparation temperature of the second fluid is 5 ° C. That is, referring to FIGS. 23 and 25, the degree of crystallinity / average particle size change and the amount of change in ⁇ -type crystal ratio / average particle size of indomethacin microparticles with respect to the preparation temperature of the second fluid are as follows. The shorter the time, the smaller. An example of the control method in this case is as follows.
  • the preparation time of the second fluid is set to a short time, and then the preparation temperature of the second fluid is set to thereby change the desired crystallinity / average particle diameter and The ⁇ -type crystal ratio / average particle diameter can be easily obtained. Further, in order to increase the crystallinity / average particle diameter and the ⁇ -type crystal ratio / average particle diameter when the preparation temperature of the second fluid is the same, the preparation time of the second fluid should be set long. In order to reduce the crystallinity / average particle diameter and ⁇ -type crystal ratio / average particle diameter, the preparation time may be set short.

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Abstract

This fine particle production method involves a dissolving step in which a stirrer having a rotating stirring blade is used to dissolve at least one type of fine particle raw material in a solvent to obtain a fine particle raw material solution, and a precipitation step in which the fine particle raw material solution and at least one type of precipitation solvent for precipitating the fine particle raw material from the fine particle raw material solution are introduced between at least two treatment surfaces which are arranged oppositely one another, can move closer to and farther apart from one another, and at least one of which can rotate relative to the other, and the fine particle raw material solution and the at least one type of precipitation solvent are mixed in a thin film fluid formed between the at least two treatment surfaces, and the fine particles are precipitated. The stirring energy is determined by the stirring time conditions of the stirrer, the circumferential velocity conditions of the stirring blade, and the temperature conditions of the fine particle raw material solution, and in the dissolving step, the stirring energy is varied by changing at least one of the aforementioned conditions, and by changing the stirring energy, the degree of crystallization and the crystal form of the fine particles obtained in the precipitation step are controlled.

Description

微粒子の製造方法Method for producing fine particles
　本発明は、微粒子の製造方法に関する。 The present invention relates to a method for producing fine particles.
　金属や酸化物、医薬品や食品、化粧品などの生体摂取物、顔料などの微粒子が、産業界における広い分野において必要とされている。 Metals, oxides, biological ingestions such as pharmaceuticals, foods and cosmetics, and fine particles such as pigments are required in a wide range of industries.
　微粒子の製造方法は、貧溶媒法や晶析、酸化や還元などの反応を、特許文献１に記載されているようなフラスコやビーカー、タンクなどを用いて行う場合が一般的であるが、そのような容器を用いた場合には、容器内における濃度や温度を均一に保つことが難しいために、得られる微粒子の粒子径分布が広くなりやすく、また２種以上の元素を含む合金や複合酸化物などの微粒子を作製する場合に、均質な元素比で微粒子を作製することが困難であった。また特許文献２に記載されているようなマイクロリアクターを用いた微粒子の製造方法も提供されているが、一般的なマイクロリアクターを用いた場合には反応物の閉塞やスケールアップが出来ないことなど現状課題が多い。そのため、均質且つ均一な微粒子を安定的且つ低エネルギー、省資源で製造する方法が懇願されていた。 The method for producing fine particles is generally performed by using a flask, beaker, tank, or the like as described in Patent Document 1 for reactions such as an anti-solvent method, crystallization, oxidation, and reduction. When such a container is used, it is difficult to keep the concentration and temperature uniform in the container, so that the particle size distribution of the resulting fine particles tends to be widened, and alloys and composite oxidations containing two or more elements When producing fine particles such as a product, it was difficult to produce fine particles with a uniform element ratio. In addition, a method for producing fine particles using a microreactor as described in Patent Document 2 is also provided. However, when a general microreactor is used, clogging of reactants and scale-up cannot be performed. There are many current issues. Therefore, a method for producing homogeneous and uniform fine particles stably, with low energy and resource saving has been appealed.
　本願出願人によって、特許文献３に記載されたような、対向して配設された、接近・離反可能な、少なくとも一方が他方に対して相対的に回転する少なくとも２つの処理用面の間にできる薄膜流体中で微粒子の原料を溶解した微粒子原料溶液と微粒子を析出させるための析出用溶媒とを混合する微粒子の製造方法が提供された。 By the applicant of the present application, as described in Patent Document 3, between at least two processing surfaces disposed opposite to each other and capable of approaching / separating, at least one rotating relative to the other. There has been provided a method for producing fine particles in which a fine particle raw material solution in which a fine particle raw material is dissolved in a thin film fluid, and a precipitation solvent for precipitating the fine particles are mixed.
　しかし、特許文献３に記載されたような方法を用いた場合であっても、安定的に微粒子を作製することが難しい場合や、２種以上の分子や元素を含む微粒子を作製する場合に、局所的な元素比にバラツキがあり、均一且つ均質な微粒子を作製する事が難しい場合があった。 However, even when the method described in Patent Document 3 is used, when it is difficult to stably produce fine particles, or when producing fine particles containing two or more kinds of molecules and elements, There are variations in local element ratios, and it may be difficult to produce uniform and uniform fine particles.
　さらに、特許文献４に記載されたような方法を併用した場合であっても、単に被処理流動体の処方や送液量、温度、処理用面の回転数といった装置の運転条件を変更するだけでは、生成される微粒子に関して所望の結晶化度、結晶型あるいは特定結晶型の構成比率を達成することが困難であり、結晶化度、結晶型あるいは特定結晶型の構成比率といった微粒子の性状／特性を自在に制御する具体的な方法までは開示されておらず、改善の余地を残していた。ここで、「特定結晶型の構成比率」とは、生成される微粒子が複数の結晶型を有する場合に、複数の結晶型の結晶成分中に、特定の結晶型の結晶成分が占める割合をいう。 Furthermore, even when the method described in Patent Document 4 is used in combination, the operating conditions of the apparatus such as the prescription of the fluid to be processed, the liquid feeding amount, the temperature, and the rotational speed of the processing surface are simply changed. Therefore, it is difficult to achieve a desired crystallinity, crystal type or specific crystal type composition ratio of the generated fine particles, and properties / characteristics of the fine particles such as crystallinity, crystal type or specific crystal type composition ratio. No specific method for freely controlling the image is disclosed, leaving room for improvement. Here, the “constituent ratio of a specific crystal type” refers to a ratio of a crystal component of a specific crystal type to a plurality of crystal components of the crystal type when the generated fine particles have a plurality of crystal types. .
特開２００２－０９７２８１号公報JP 2002-097281 A 特開２００６－１９３６５２号公報JP 2006-193652 A 国際公開ＷＯ２００９／００８３９３号パンフレットInternational Publication WO2009 / 008393 Pamphlet 国際公開ＷＯ２０１２／１２８２７３号パンフレットInternational Publication WO2012 / 128273 Pamphlet
　本発明は、前記のような状況を鑑みてなされたものであり、結晶化度、結晶型あるいは特定結晶型の構成比率といった性状／特性に関して所望の微粒子を得ることができる製造方法を提供することを目的とする。 The present invention has been made in view of the above situation, and provides a production method capable of obtaining desired fine particles with respect to properties / characteristics such as crystallinity, crystal type, or composition ratio of a specific crystal type. With the goal.
　本発明の微粒子の製造方法は、回転する攪拌翼を有する攪拌機を用いて、少なくとも１種類の微粒子原料を溶媒に溶解させて微粒子原料溶液を得る溶解ステップと、前記微粒子原料溶液から前記微粒子原料を析出させるための少なくとも１種類の析出溶媒と、前記微粒子原料溶液とを、対向して配設された、接近・離反可能な、少なくとも一方が他方に対して相対的に回転する少なくとも２つの処理用面間に導入し、前記少なくとも２つの処理用面間に形成される薄膜流体中で混合して、微粒子を析出させる析出ステップとを備えるものである。
　そして、前記溶解ステップにて、前記攪拌機による攪拌時間条件、前記攪拌翼の周速度条件、前記微粒子原料溶液の温度条件とにて規定される攪拌エネルギーを、前記条件のうち少なくとも１つを変化させることにより、増減させ、前記攪拌エネルギーの増減によって、前記析出ステップで得られる前記微粒子の結晶化度を制御することを要旨とする。 The method for producing fine particles of the present invention comprises a dissolving step of dissolving at least one kind of fine particle raw material in a solvent using a stirrer having a rotating stirring blade, and obtaining the fine particle raw material solution from the fine particle raw material solution. At least two types of deposition solvents for depositing and the fine particle raw material solution disposed opposite to each other and capable of approaching / separating at least one rotating relative to the other. A deposition step of introducing between the surfaces and mixing in a thin film fluid formed between the at least two processing surfaces to precipitate fine particles.
In the dissolving step, at least one of the above conditions is changed in the stirring energy defined by the stirring time condition by the stirrer, the peripheral speed condition of the stirring blade, and the temperature condition of the fine particle raw material solution Thus, the gist is to control the crystallinity of the fine particles obtained in the precipitation step by increasing or decreasing the stirring energy.
　また、前記溶解ステップにて、前記攪拌機による攪拌時間条件、前記攪拌翼の周速度条件、前記微粒子原料溶液の温度条件とにて規定される攪拌エネルギーを、前記条件のうち少なくとも１つを変化させることにより、増減させ、前記攪拌エネルギーの増減によって、前記析出ステップで得られる前記微粒子の結晶型を制御することを要旨とする。
　また、前記溶解ステップにて、前記攪拌機による攪拌時間条件、前記攪拌翼の周速度条件、前記微粒子原料溶液の温度条件とにて規定される攪拌エネルギーを、前記条件のうち少なくとも１つを変化させることにより、増減させ、前記攪拌エネルギーの増減によって、前記析出ステップで得られる前記微粒子の結晶化度と結晶型との両方を制御するものとして実施してもよい。
　ここで、攪拌エネルギーについて、より詳しく説明する。
　先ず、撹拌機の動力P（単位時間あたりの仕事量）は次の式（１）で求められる。
攪拌動力P[kw]＝Np×ρ×n3×d5・・・式（１）
Np：動力係数（実験データから算出される無次元数。
例えば、後述のクレアミックス（エム・テクニック株式会社製）の場合はNp＝0.95～1.05である。
ρ：密度[kg／m3]　
n：回転数[rps]　
d：ローター径[m]
　次に、撹拌エネルギー（即ち、撹拌のために投下したエネルギー）は、撹拌動力と撹拌時間との積（撹拌動力P[kw]×撹拌時間t[s]）で表せることから、
撹拌エネルギー＝Np×ρ×n3×d5×t・・・式（２）
となる。
　さらに、周速度v=π×d×nの関係があるため、上記の式（２）はつぎのように書きかえられる。
攪拌エネルギー＝Np×(1/π3)×ρ×v3×d2×t・・・式（３）
　ここで、原料溶液の処理量、原料溶液を収容した容器サイズが統一され、同一の撹拌機を使用するならば、同一の系として見做すことができ、ローター径d[m]は一定となるため、Np×(1/π3)×d2は、定数として扱うことがきる。
　一般の液体は、温度が上昇すると膨張して体積が増加するので密度が小さくなり、温度が低下すると収縮して体積が減少するので密度が大きくなるため、原料溶液の密度は温度によって変化する。すなわち、原料溶液の密度は温度に依存する。
　従って、式（３）より、撹拌エネルギーは、攪拌時間条件、撹拌翼の周速度条件、微粒子原料溶液の温度条件で規定されることになる。 Further, in the dissolving step, at least one of the above conditions is changed in the stirring energy defined by the stirring time condition by the stirrer, the peripheral speed condition of the stirring blade, and the temperature condition of the fine particle raw material solution Thus, the gist is to control the crystal form of the fine particles obtained in the precipitation step by increasing or decreasing the stirring energy.
Further, in the dissolving step, at least one of the above conditions is changed in the stirring energy defined by the stirring time condition by the stirrer, the peripheral speed condition of the stirring blade, and the temperature condition of the fine particle raw material solution Accordingly, the present invention may be carried out by controlling both the crystallinity and the crystal form of the fine particles obtained in the precipitation step by increasing or decreasing the stirring energy.
Here, the stirring energy will be described in more detail.
First, the power P (work per unit time) of the stirrer is obtained by the following formula (1).
Stirring power P [kw] = Np × ρ × n 3 × d 5 (1)
Np: Power coefficient (a dimensionless number calculated from experimental data.
For example, Np = 0.95 to 1.05 in the case of CLEARMIX (made by M Technique Co., Ltd.) described later.
ρ: Density [kg / m 3 ]
n: Number of revolutions [rps]
d: Rotor diameter [m]
Next, since the stirring energy (that is, energy dropped for stirring) can be expressed by the product of stirring power and stirring time (stirring power P [kw] × stirring time t [s]),
Stirring energy = Np × ρ × n 3 × d 5 × t Equation (2)
It becomes.
Furthermore, since there is a relationship of peripheral speed v = π × d × n, the above equation (2) can be rewritten as follows.
Stirring energy = Np × (1 / π 3 ) × ρ × v 3 × d 2 × t Equation (3)
Here, if the processing amount of the raw material solution and the size of the container containing the raw material solution are unified and the same stirrer is used, it can be regarded as the same system, and the rotor diameter d [m] is constant. Therefore, Np × (1 / π 3 ) × d 2 can be treated as a constant.
A general liquid expands and increases in volume when the temperature rises, and thus decreases in density. When the temperature decreases, the volume contracts and decreases in volume, so that the density increases. Therefore, the density of the raw material solution varies depending on the temperature. That is, the density of the raw material solution depends on the temperature.
Therefore, from the formula (3), the stirring energy is defined by the stirring time condition, the peripheral speed condition of the stirring blade, and the temperature condition of the fine particle raw material solution.
　また、前記析出ステップにおける前記微粒子の析出方法は特に問わないが、代表的なものとしてアシッドペースティング法、アルカリペースト法、貧溶媒法を例示すことができる。そして、前記に例示した析出方法に代表される析出方法による析出ステップに先立ち、前記溶解ステップにおける前記攪拌エネルギーを増加させることにより、前記微粒子の粒子径に対する前記微粒子の結晶化度の比率が上昇するように制御するものとして実施することができる。
　また、本発明は、前記に例示した析出方法に代表される種々の析出方法による析出ステップにより前記微粒子を析出するものであり、前記微粒子は複数の結晶型を有し、複数の結晶型の結晶成分に対する特定の結晶型の結晶成分の比率を特定結晶型の構成比率とするものであり、前記溶解ステップにおける前記攪拌エネルギーを増加させることにより、前記微粒子の粒子径に対する前記特定結晶型の構成比率の比率が上昇するように制御するものとして実施することができる。 Moreover, the precipitation method of the fine particles in the precipitation step is not particularly limited, but typical examples include an acid pasting method, an alkali paste method, and a poor solvent method. Then, prior to the precipitation step by the precipitation method represented by the precipitation method exemplified above, the ratio of the crystallinity of the fine particles to the particle diameter of the fine particles is increased by increasing the stirring energy in the dissolution step. It can implement as what controls.
Further, the present invention deposits the fine particles by a precipitation step by various precipitation methods typified by the precipitation method exemplified above, and the fine particles have a plurality of crystal types, and a plurality of crystal type crystals. The ratio of the crystal component of the specific crystal type to the component is the specific crystal type constituent ratio, and the constituent ratio of the specific crystal type to the particle diameter of the fine particles is increased by increasing the stirring energy in the dissolving step. It can implement as what controls so that the ratio of may rise.
　また、本発明は、前記微粒子が、顔料微粒子であるものとして実施することができる。
　顔料微粒子は、塗料、印刷インク、トナー、インクジェットインク、カラーフィルター等の非常に様々な分野で利用されているが、特に、実用上高機能の材料が必要とされている分野の一つとして、イメージセンサ用カラーフィルターや液晶ディスプレイ（以下、ＬＣＤ）用カラーフィルターがある。ＬＣＤ用カラーフィルター用顔料には、高い透過率特性が要求され、透過率特性に関する指標として「結晶化度」、「特定結晶型の構成比率」がある。これらの指標を制御することによって、透過率が高い顔料微粒子を得ることが可能になる。
　また、インクジェットインクやトナー用顔料の場合には、色目や着色力、耐久性が要求され、それらを評価する指標としても、「結晶化度」、「特定結晶型の構成比率」がある。
　一例として、２，９－ジメチルキナクリドン（Ｃ．Ｉ．Ｐｉｇｍｅｎｔ　Ｒｅｄ　１２２）（以下、ＰＲ１２２と記載する）の結晶型には、α型結晶とβ型結晶とが存在し、通常両者が混在するが、β型結晶が安定型、α型結晶が準安定型である。α型結晶の占める比率が高いほど黄身がかっており、目的の色調によって結晶型の比率を作り分ける必要がある。このように、ＰＲ１２２におけるα型結晶とβ型結晶を合わせた結晶成分中に、α型結晶、またはβ型結晶が占める割合を「特定結晶型の構成比率」と称し、なかでもＰＲ１２２におけるα型結晶とβ型結晶を合わせた結晶成分中に、β型結晶が占める割合を「β型結晶比率」と称している。
　また、ＰＲ１２２全体では、結晶成分と非晶質（アモルファス）とが混在し、結晶化した成分と非晶質を合わせた全体に対して結晶化した成分の占める割合を「結晶化度」と称し、通常、結晶化度が高い程、光や熱、湿気等に対する耐久性が向上し、これは周知である。
　つまり、溶解ステップにおける攪拌エネルギーの増減によって析出ステップで得られる微粒子の結晶化度を制御し、また、溶解ステップにおける攪拌エネルギーの増減によって析出ステップで得られる微粒子の特定結晶型の構成比率を制御することによって、インクジェットインクとして用いるＰＲ１２２微粒子は、「結晶化度」が高く、かつ「α型結晶比率」と「β型結晶比率」を目的の色調によって作り分ける必要がある。
　また、本発明は、前記微粒子が、顔料微粒子以外であるものとして実施することができ、医薬品であるインドメタシンにあっては、溶解ステップにおける攪拌エネルギーの増減によって析出ステップで得られる微粒子の結晶化度を制御し、また、溶解ステップにおける攪拌エネルギーの増減によって析出ステップで得られる微粒子の特定結晶型の構成比率を制御することによって、結晶化度や結晶型といった性状／特性に関して、所望のインドメタシン微粒子を得ることができる。
　インドメタシンは複数の結晶型を有し、代表的なものに安定型のγ型結晶、不安定型のα型結晶、準安定型のβ型結晶がある。通常それらの結晶型は混在するが、γ型結晶の占める比率が高いほど安定した特性である。このように、インドメタシンにおけるγ型結晶、α型結晶及びβ型結晶を合わせた結晶成分中に、γ型結晶、α型結晶、またはβ型結晶が占める割合を「特定結晶型の構成比率」と称し、なかでもインドメタシンにおけるγ型結晶、α型結晶及びβ型結晶を合わせた結晶成分中に、γ型結晶が占める割合を「γ型結晶比率」と称している。
　顔料であるＰＲ１２２や医薬品であるインドメタシンのように、用途の異なる化合物であっても、溶解ステップにおける攪拌エネルギーの増減によって析出ステップで得られる微粒子の結晶化度を制御し、また、溶解ステップにおける攪拌エネルギーの増減によって析出ステップで得られる微粒子の結晶型を制御できることから、他の物質にあっても同様の傾向を示すものと考えられる。
　本発明は、溶解ステップにて物理的なエネルギーである攪拌エネルギーを増減させることによって、所謂溶けている状態を制御する、言い換えれば微粒子原料溶液の溶解状態を変化させたり、クラスター形成状態を変化させたり、分子レベルでの溶解状態もしくは分子分散状態である微粒子原料溶液を調製することができたことから、その後の処理である析出ステップで得られる微粒子の結晶化度や結晶型（複数の結晶型を有するものにあっては、特定結晶型の構成比率）を制御することができたものである。よって、微粒子原料溶液の調整においては、化合物を構成する物質の種類や化学的な反応の種類が変わっても特段影響を受けないものであるから、ＰＲ１２２やインドメタシン以外の他の物質にあっても同様の傾向を示すものと考えられる。 In addition, the present invention can be carried out with the fine particles being pigment fine particles.
Pigment fine particles are used in a wide variety of fields such as paints, printing inks, toners, inkjet inks, color filters, etc., but in particular, as one of the fields where highly functional materials are required in practice, There are color filters for image sensors and color filters for liquid crystal displays (hereinafter, LCDs). The color filter pigments for LCDs are required to have high transmittance characteristics, and there are “crystallinity” and “constituent ratio of specific crystal type” as indices relating to the transmittance characteristics. By controlling these indicators, it is possible to obtain pigment fine particles with high transmittance.
In addition, in the case of inkjet inks and toner pigments, color, coloring power, and durability are required, and indexes for evaluating them include “crystallinity” and “specific crystal component ratio”.
As an example, the crystal type of 2,9-dimethylquinacridone (CI Pigment Red 122) (hereinafter referred to as PR122) includes an α-type crystal and a β-type crystal, and both are usually mixed. Β-type crystals are stable, and α-type crystals are metastable. The higher the proportion occupied by α-type crystals, the more yellow the yolk is, and it is necessary to create crystal proportions according to the target color tone. Thus, the proportion of the α-type crystal or β-type crystal in the crystal component of the α-type crystal and the β-type crystal in PR122 is referred to as “constituent ratio of the specific crystal type”. The ratio of the β-type crystal to the total crystal component of the crystal and the β-type crystal is called “β-type crystal ratio”.
Further, in the entire PR122, a crystal component and an amorphous component are mixed, and the ratio of the crystallized component to the total of the crystallized component and the amorphous component is referred to as “crystallinity”. In general, the higher the crystallinity, the better the durability against light, heat, moisture, etc., which is well known.
That is, the degree of crystallinity of the fine particles obtained in the precipitation step is controlled by increasing or decreasing the stirring energy in the dissolution step, and the specific crystal type composition ratio of the fine particles obtained in the precipitation step is controlled by increasing or decreasing the stirring energy in the dissolving step. Accordingly, the PR122 fine particles used as the ink-jet ink have a high “crystallinity”, and it is necessary to make “α-type crystal ratio” and “β-type crystal ratio” separately according to the target color tone.
In addition, the present invention can be carried out as the fine particles are other than pigment fine particles. In the case of indomethacin, which is a pharmaceutical, the crystallinity of the fine particles obtained in the precipitation step by increasing or decreasing the stirring energy in the dissolution step. In addition, by controlling the composition ratio of the specific crystal form of the fine particles obtained in the precipitation step by increasing or decreasing the stirring energy in the dissolution step, the desired indomethacin fine particles can be obtained in terms of properties / characteristics such as crystallinity and crystal form. Obtainable.
Indomethacin has a plurality of crystal types, and representative examples include a stable γ-type crystal, an unstable α-type crystal, and a metastable β-type crystal. Usually, these crystal forms coexist, but the higher the proportion of γ-type crystals, the more stable characteristics. As described above, the proportion of the γ-type crystal, α-type crystal, or β-type crystal in the crystal component of γ-type crystal, α-type crystal, and β-type crystal in indomethacin is referred to as the “constituent ratio of the specific crystal type”. In particular, the proportion of γ-type crystals in the crystal component of γ-type crystals, α-type crystals, and β-type crystals in indomethacin is called “γ-type crystal ratio”.
Even for compounds with different uses, such as PR122, which is a pigment, and indomethacin, which is a pharmaceutical, the degree of crystallinity of fine particles obtained in the precipitation step is controlled by increasing or decreasing the stirring energy in the dissolving step, and stirring in the dissolving step. Since the crystal form of the fine particles obtained in the precipitation step can be controlled by increasing or decreasing the energy, it is considered that the same tendency is exhibited even in other substances.
The present invention controls the so-called dissolved state by increasing or decreasing the stirring energy, which is physical energy, in the dissolving step, in other words, changing the dissolved state of the fine particle raw material solution or changing the cluster forming state. In addition, it was possible to prepare a fine particle raw material solution in a dissolved state or a molecular dispersed state at a molecular level, so that the degree of crystallinity and crystal type of the fine particles obtained in the subsequent precipitation step (multiple crystal types) The composition ratio of the specific crystal type) can be controlled. Therefore, in the preparation of the fine particle raw material solution, even if the substance constituting the compound or the kind of chemical reaction is not affected, it is not particularly affected. It is thought that the same tendency is shown.
　また、本発明は、粒子径、結晶化度及び結晶型が特定条件に設定された微粒子を製造するに際して、前記溶解ステップにおける前記周速度条件と前記攪拌時間条件と前記温度条件とのうち１つの条件（第１条件）を変化させ、他の２つの条件（第２第３条件）を固定することにより、前記析出ステップにおける前記微粒子の粒子径、結晶化度及び結晶型のうちの少なくとも１つについて前記特定条件を充足する前記第１条件を決定する。決定された前記第１条件を維持しながら、前記第２第３条件のうち少なくとも何れか一方を変化させることにより、前記析出ステップにおける前記微粒子の粒子径、結晶化度及び結晶型のうちの前記少なくとも１つとは異なる残りの２つについて、前記第２第３条件のうち少なくとも何れか一方の条件を決定することによって、粒子径、結晶化度及び結晶型が前記特定条件を充足する微粒子を製造するものとして実施することができる。
　一例としては、粒子径、結晶化度及び結晶型が特定条件に設定された微粒子を製造するに際して、前記溶解ステップにおける前記攪拌翼の周速度条件を変化させることにより、前記析出ステップにおける前記微粒子の粒子径についての前記特定条件を充足する前記周速度条件を決定し、決定された前記周速度条件を維持しながら、前記攪拌時間条件と前記温度条件との少なくとも何れか一方を変化させることにより、前記析出ステップにおける前記微粒子の結晶化度及び結晶型についての前記特定条件を充足する前記攪拌時間条件と前記温度条件を決定することによって、粒子径、結晶化度及び結晶型が前記特定条件を充足する微粒子を製造するものとして実施することができる。 Further, the present invention provides one of the peripheral speed condition, the stirring time condition, and the temperature condition in the dissolving step when producing fine particles having a particle diameter, a crystallinity, and a crystal type set to specific conditions. By changing the condition (first condition) and fixing the other two conditions (second third condition), at least one of the particle diameter, crystallinity, and crystal type of the fine particles in the precipitation step The first condition that satisfies the specific condition is determined. By changing at least one of the second and third conditions while maintaining the determined first condition, the particle size, crystallinity, and crystal type of the fine particles in the precipitation step are changed. Manufacturing at least one of the second and third conditions for the remaining two different from at least one to produce fine particles satisfying the specific conditions in terms of particle diameter, crystallinity and crystal type Can be implemented.
As an example, when producing microparticles whose particle diameter, crystallinity, and crystal type are set to specific conditions, by changing the peripheral speed condition of the stirring blade in the dissolution step, the microparticles in the precipitation step By determining the peripheral speed condition that satisfies the specific condition for the particle diameter, and maintaining the determined peripheral speed condition, by changing at least one of the stirring time condition and the temperature condition, By determining the stirring time condition and the temperature condition satisfying the specific conditions for the crystallinity and crystal form of the fine particles in the precipitation step, the particle diameter, the crystallinity, and the crystal form satisfy the specific conditions. It can be carried out as a method for producing fine particles.
　前記本発明の実施の態様の単なる一例を示せば、少なくとも２種類の被処理流動体を用いるものであり、そのうちで少なくとも１種類の被処理流動体については前記微粒子原料溶液であり、前記微粒子原料溶液以外の被処理流動体のうちで少なくとも１種類の被処理流動体については前記析出溶媒であり、被処理流動体に圧力を付与する流体圧付与機構と、前記少なくとも２つの処理用面のうち第１処理用面を備えた第１処理用部と、前記少なくとも２つの処理用面のうち第２処理用面を備えた第２処理用部とを備え、これらの処理用部を相対的に回転させる回転駆動機構とを備え、前記の各処理用面は、前記の圧力が付与された被処理流動体が流される、密封された流路の一部を構成するものであり、前記第１処理用部と第２処理用部のうち、少なくとも第２処理用部は受圧面を備えるものであり、且つ、この受圧面の少なくとも一部が前記第２処理用面により構成され、この受圧面は、前記の流体圧付与機構が被処理流動体に付与する圧力を受けて第１処理用面から第２処理用面を離反させる方向に移動させる力を発生させ、対向して配設された、接近・離反可能な、少なくとも一方が他方に対して相対的に回転する第１処理用面と第２処理用面との間に前記の圧力が付与された被処理流動体が通されることにより、前記被処理流動体が前記薄膜流体を形成し、この薄膜流体中において微粒子を析出させる微粒子の製造方法として実施することができる。 If only one example of the embodiment of the present invention is shown, at least two kinds of fluids to be treated are used, and at least one kind of fluid to be treated is the fine particle raw material solution, and the fine particle raw materials are Among the fluids to be treated other than the solution, at least one kind of fluid to be treated is the precipitation solvent, and a fluid pressure imparting mechanism for imparting pressure to the fluid to be treated, and among the at least two processing surfaces A first processing part having a first processing surface, and a second processing part having a second processing surface of the at least two processing surfaces, the processing parts being relatively Each of the processing surfaces constitutes a part of a sealed flow path through which the fluid to be processed to which the pressure is applied flows. Of the processing part and the second processing part. That is, at least the second processing portion includes a pressure receiving surface, and at least a part of the pressure receiving surface is constituted by the second processing surface, and the pressure receiving surface is covered by the fluid pressure applying mechanism. Upon receiving the pressure applied to the processing fluid, a force is generated to move the second processing surface away from the first processing surface, and at least one of the facing and disengagement disposed is opposed. The fluid to be processed is passed between the first processing surface and the second processing surface that rotate relative to the other, so that the fluid to be processed is the thin film. It can be implemented as a method for producing fine particles in which a fluid is formed and fine particles are precipitated in the thin film fluid.
　また、前記本発明の実施の態様の単なる一例を示せば、前記の被処理流動体のうちの少なくともいずれか１種の流体が前記薄膜流体を形成しながら前記両処理用面間を通過し、前記少なくともいずれか１種の流体が流される流路とは独立した別途の導入路を備えており、前記第１処理用面と第２処理用面の少なくとも何れか一方が、前記の導入路に通じる開口部を少なくとも一つ備え、前記少なくともいずれか１種の流体とは異なる少なくとも１種の流体を、前記開口部から前記処理用面の間に導入し、前記の被処理流動体を前記薄膜流体中で混合し、この薄膜流体中において微粒子を析出させる微粒子の製造方法として実施することができる。 Further, if only one example of the embodiment of the present invention is shown, at least any one of the fluids to be processed passes between the processing surfaces while forming the thin film fluid, A separate introduction path independent of the flow path through which at least one of the fluids flows is provided, and at least one of the first processing surface and the second processing surface is in the introduction path. At least one opening that communicates, and at least one fluid different from the at least one fluid is introduced between the processing surfaces from the opening, and the fluid to be treated is placed in the thin film It can be implemented as a method of producing fine particles that are mixed in a fluid and fine particles are precipitated in the thin film fluid.
　本発明は、微粒子の結晶化度や結晶型の制御を可能とし、結晶化度や結晶型を制御された微粒子を連続して製造することができる。
　また、本発明は、微粒子原料溶液の調製を、回転する攪拌翼を有する攪拌機を用いて行い、その際に、攪拌エネルギーを規定する３つの条件（攪拌時間、攪拌翼の周速度、微粒子原料溶液の温度）のうち少なくとも１つを変化させることにより、攪拌エネルギーを増減させるという簡単な処理条件の変更によって、所謂溶けている状態を制御する、言い換えれば微粒子原料溶液の溶解状態を変化させたり、クラスター形成状態を変化させたり、分子レベルでの溶解状態もしくは分子分散状態である微粒子原料溶液を調製することができたことから、その後の析出ステップで析出させた微粒子の結晶化度や結晶型を制御することができ、結晶化度や結晶型といった性状／特性に関して、所望の微粒子を得ることができる。
　さらに、目的に応じた微粒子を作り分けることができる。 The present invention makes it possible to control the crystallinity and crystal form of fine particles, and to continuously produce fine particles with controlled crystallinity and crystal form.
In the present invention, the fine particle raw material solution is prepared by using a stirrer having a rotating stirring blade, and at that time, three conditions (the stirring time, the peripheral speed of the stirring blade, and the fine particle raw material solution are defined. By changing at least one of the temperature), the so-called dissolved state is controlled by simply changing the processing conditions of increasing or decreasing the stirring energy, in other words, changing the dissolved state of the fine particle raw material solution, Since it was possible to change the cluster formation state and to prepare a fine particle raw material solution that was dissolved or dispersed at the molecular level, the crystallinity and crystal form of the fine particles deposited in the subsequent precipitation step The desired fine particles can be obtained with respect to properties / characteristics such as crystallinity and crystal form.
Furthermore, it is possible to make fine particles according to the purpose.
本発明の実施の形態に係る流体処理装置の略断面図である。1 is a schematic cross-sectional view of a fluid processing apparatus according to an embodiment of the present invention. （Ａ）は図１に示す流体処理装置の第１処理用面の略平面図であり、（Ｂ）は同装置の処理用面の要部拡大図である。(A) is a schematic plan view of a first processing surface of the fluid processing apparatus shown in FIG. 1, and (B) is an enlarged view of a main part of the processing surface of the apparatus. （Ａ）は同装置の第２導入部の断面図であり、（Ｂ）は同第２導入部を説明するための処理用面の要部拡大図である。(A) is sectional drawing of the 2nd introducing | transducing part of the apparatus, (B) is the principal part enlarged view of the processing surface for demonstrating the 2nd introducing | transducing part. 本発明の実施の形態に係る回転する攪拌翼を有する攪拌機の正面図である。It is a front view of the stirrer which has the rotating stirring blade which concerns on embodiment of this invention. 同攪拌機の内部構造説明図である。It is internal structure explanatory drawing of the stirrer. 実施例１～３にて第２流体の調製温度に対するＰＲ１２２微粒子の結晶化度／平均粒子径及びβ型結晶比率／平均粒子径の変化を示すグラフである。4 is a graph showing changes in crystallinity / average particle diameter and β-type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation temperature of the second fluid in Examples 1 to 3. 実施例４～７にて第２流体の調製時間に対するＰＲ１２２微粒子の結晶化度／平均粒子径及びβ型結晶比率／平均粒子径の変化を示すグラフである。6 is a graph showing changes in crystallinity / average particle diameter and β-type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid in Examples 4 to 7. 実施例８～１１にて第２流体の調製時間に対するＰＲ１２２微粒子の結晶化度／平均粒子径及びβ型結晶比率／平均粒子径の変化を示すグラフである。6 is a graph showing changes in crystallinity / average particle diameter and β-type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid in Examples 8 to 11. 実施例１２～１６にて第２流体の調製時間に対するＰＲ１２２微粒子の結晶化度／平均粒子径及びβ型結晶比率／平均粒子径の変化を示すグラフである。7 is a graph showing changes in the degree of crystallinity / average particle size and β-type crystal ratio / average particle size of PR122 fine particles with respect to the preparation time of the second fluid in Examples 12 to 16. 実施例８～１１、実施例１２、１３、１５、１６にて、第２流体の調製時間に対するＰＲ１２２微粒子の結晶化度／平均粒子径の変化を示すグラフである。6 is a graph showing changes in crystallinity / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid in Examples 8 to 11 and Examples 12, 13, 15, and 16. 実施例８～１１、実施例１２、１３、１５、１６にて、第２流体の調製時間に対するＰＲ１２２微粒子のβ型結晶比率／平均粒子径の変化を示すグラフである。6 is a graph showing changes in β-type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid in Examples 8 to 11 and Examples 12, 13, 15, and 16. 実施例１７～２２にて第２流体調製時の周速度に対するＰＲ１２２微粒子の結晶化度／平均粒子径の変化を示すグラフである。6 is a graph showing changes in crystallinity / average particle diameter of PR122 fine particles with respect to the peripheral speed at the time of preparing the second fluid in Examples 17-22. 実施例１７～２２にて第２流体調製時の周速度に対するＰＲ１２２微粒子のβ型結晶比率／平均粒子径の変化を示すグラフである。6 is a graph showing changes in β-type crystal ratio / average particle diameter of PR122 fine particles with respect to the peripheral speed at the time of preparing the second fluid in Examples 17-22. 実施例２３～３１にて第２流体の調製時間に対するＰＲ１２２微粒子の結晶化度／平均粒子径の変化を示すグラフである。6 is a graph showing changes in the crystallinity / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid in Examples 23 to 31. 実施例２３～３１にて第２流体の調製時間に対するＰＲ１２２微粒子のβ型結晶比率／平均粒子径の変化を示すグラフである。6 is a graph showing changes in β-type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid in Examples 23 to 31. 実施例２３～３１にて第２流体の調製温度に対するＰＲ１２２微粒子の結晶化度／平均粒子径の変化を示すグラフである。FIG. 10 is a graph showing changes in crystallinity / average particle diameter of PR122 fine particles with respect to the preparation temperature of the second fluid in Examples 23 to 31. FIG. 実施例２３～３１にて第２流体の調製温度に対するＰＲ１２２微粒子のβ型結晶比率／平均粒子径の変化を示すグラフである。FIG. 10 is a graph showing changes in β-type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation temperature of the second fluid in Examples 23 to 31. FIG. 実施例３２～４０にて第２流体の調製時間に対するＰＲ１２２微粒子の結晶化度／平均粒子径の変化を示すグラフである。4 is a graph showing the change in crystallinity / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid in Examples 32 to 40. 実施例３２～４０にて第２流体の調製時間に対するＰＲ１２２微粒子のβ型結晶比率／平均粒子径の変化を示すグラフである。40 is a graph showing changes in β-type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid in Examples 32 to 40. 実施例３２～４０にて第２流体の調製温度に対するＰＲ１２２微粒子の結晶化度／平均粒子径の変化を示すグラフである。4 is a graph showing the change in crystallinity / average particle diameter of PR122 fine particles with respect to the preparation temperature of the second fluid in Examples 32 to 40. 実施例３２～４０にて第２流体の調製温度に対するＰＲ１２２微粒子のβ型結晶比率／平均粒子径の変化を示すグラフである。40 is a graph showing changes in β-type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation temperature of the second fluid in Examples 32 to 40. 実施例４１～４９にて第２流体の調製時間に対するインドメタシン微粒子の結晶化度／平均粒子径の変化を示すグラフである。FIG. 6 is a graph showing changes in crystallinity / average particle diameter of indomethacin fine particles with respect to the preparation time of the second fluid in Examples 41 to 49. FIG. 実施例４１～４９にて第２流体の調製温度に対するインドメタシン微粒子の結晶化度／平均粒子径の変化を示すグラフである。FIG. 6 is a graph showing changes in crystallinity / average particle diameter of indomethacin fine particles with respect to the preparation temperature of the second fluid in Examples 41 to 49. FIG. 実施例４１～４９にて第２流体の調製時間に対するインドメタシン微粒子のγ型結晶比率／平均粒子径の変化を示すグラフである。FIG. 6 is a graph showing changes in γ-type crystal ratio / average particle diameter of indomethacin fine particles with respect to the preparation time of the second fluid in Examples 41 to 49. FIG. 実施例４１～４９にて第２流体の調製温度に対するインドメタシン微粒子γ型結晶比率／平均粒子径の変化を示すグラフである。FIG. 10 is a graph showing changes in indomethacin fine particle γ-type crystal ratio / average particle diameter with respect to the preparation temperature of the second fluid in Examples 41 to 49. FIG.
　以下、本発明について詳細を説明する。しかし、本発明の技術的範囲は、下記実施形態及び実施例によって限定されるものではない。 Hereinafter, the details of the present invention will be described. However, the technical scope of the present invention is not limited by the following embodiments and examples.
　本発明における微粒子の種類としては特に限定されない、一例としては有機物や無機物、有機無機の複合物などが挙げられる。その他としては金属及び／または非金属や、それらの化合物などが挙げられる。金属及び／または非金属の化合物としては特に限定されないが、一例を挙げると、金属または非金属の塩、酸化物、水酸化物、水酸化酸化物、窒化物、炭化物、錯体、有機塩、有機錯体、有機化合物またはそれらの水和物、有機溶媒和物などが挙げられる。特に限定されないが、金属または非金属の硝酸塩や亜硝酸塩、硫酸塩や亜硫酸塩、蟻酸塩や酢酸塩、リン酸塩や亜リン酸塩、次亜リン酸塩や塩化物、オキシ塩やアセチルアセトナート塩またはそれらの水和物、有機溶媒和物などが挙げられる。 The type of fine particles in the present invention is not particularly limited, and examples thereof include organic substances, inorganic substances, and organic-inorganic composites. Other examples include metals and / or non-metals and compounds thereof. Although it does not specifically limit as a metal and / or a nonmetallic compound, For example, a metal or a nonmetallic salt, an oxide, a hydroxide, a hydroxide oxide, a nitride, a carbide, a complex, an organic salt, an organic Complexes, organic compounds or their hydrates, organic solvates and the like can be mentioned. Without limitation, metal or non-metal nitrates and nitrites, sulfates and sulfites, formates and acetates, phosphates and phosphites, hypophosphites and chlorides, oxy salts and acetylacetates Examples thereof include narate salts, hydrates thereof, and organic solvates.
　本発明においては、前記微粒子を析出や沈殿または晶析させるための貧溶媒法や酸化反応、還元反応などの反応を、対向して配設された、接近・離反可能な、少なくとも一方が他方に対して相対的に回転する少なくとも２つの処理用面間に形成される薄膜流体中において行うことによって、微粒子を作製できる。具体的には、目的とする微粒子の原料である微粒子原料を溶媒に混合または溶解した微粒子原料溶液と、微粒子原料溶液から微粒子原料を析出させるための析出溶媒とを、対向して配設された、接近・離反可能な、少なくとも一方が他方に対して相対的に回転する少なくとも２つの処理用面間に導入し、前記少なくとも２つの処理用面間に形成される薄膜流体中で混合することによって、微粒子を析出させる。 In the present invention, an anti-solvent method for precipitating, precipitating or crystallizing the fine particles, a reaction such as an oxidation reaction, a reduction reaction, and the like, which are arranged to face each other, can be approached and separated, and at least one is on the other side. By carrying out in a thin film fluid formed between at least two processing surfaces that rotate relative to each other, fine particles can be produced. Specifically, a fine particle raw material solution obtained by mixing or dissolving a fine particle raw material that is a target fine particle raw material in a solvent, and a precipitation solvent for precipitating the fine particle raw material from the fine particle raw material solution are arranged to face each other. By introducing between at least two processing surfaces, which can be approached and separated, wherein at least one rotates relative to the other, and mixing in a thin film fluid formed between the at least two processing surfaces To deposit fine particles.
　本発明における微粒子原料としては、前記に挙げたような微粒子と同じものを用いることが可能である。本発明における微粒子原料溶液は、少なくとも１種類の微粒子原料を溶媒に混合または溶解（以下、単に、溶解とする。）することによって得る。望ましくは、少なくとも１種類の微粒子原料を溶媒に溶解または分散させて実施するものとする。 As the fine particle raw material in the present invention, the same fine particles as those mentioned above can be used. The fine particle material solution in the present invention is obtained by mixing or dissolving (hereinafter simply referred to as dissolution) at least one kind of fine particle material in a solvent. Desirably, it is carried out by dissolving or dispersing at least one kind of fine particle raw material in a solvent.
　本発明における微粒子原料として顔料を用いる場合には、特に限定されないが、一例を挙げると、有機顔料、無機顔料、有機無機複合顔料、Ｔｈｅ Ｓｏｃｉｅｔｙ ｏｆ Ｄｙｅｒｓ ａｎｄ Ｃｏｌｏｒｉｓｔｓに登録されている全ての顔料などが挙げられる。 When the pigment is used as the raw material for fine particles in the present invention, it is not particularly limited. For example, organic pigments, inorganic pigments, organic-inorganic composite pigments, all pigments registered in The Society of Dyers and Colorists, etc. Can be mentioned.
　本発明における有機顔料としては、特に限定されないが、一例を挙げると、ペリレン化合物顔料、ペリノン化合物顔料、キナクリドン化合物顔料、キナクリドンキノン化合物顔料、アントラキノン化合物顔料、アントアントロン化合物顔料、ベンズイミダゾロン化合物顔料、ジスアゾ縮合化合物顔料、ジスアゾ化合物顔料、アゾ化合物顔料、インダントロン化合物顔料、フタロシアニン化合物顔料、トリアリールカルボニウム化合物顔料、ジオキサジン化合物顔料、アミノアントラキノン化合物顔料、チオインジゴ化合物顔料、イソインドリン化合物顔料、イソインドリノン化合物顔料、ピラントロン化合物顔料、イソビオラントロン化合物顔料、またはそれらの混合物が挙げられる。 The organic pigment in the present invention is not particularly limited, but for example, perylene compound pigment, perinone compound pigment, quinacridone compound pigment, quinacridone quinone compound pigment, anthraquinone compound pigment, anthanthrone compound pigment, benzimidazolone compound pigment, Disazo condensation compound pigment, disazo compound pigment, azo compound pigment, indanthrone compound pigment, phthalocyanine compound pigment, triarylcarbonium compound pigment, dioxazine compound pigment, aminoanthraquinone compound pigment, thioindigo compound pigment, isoindoline compound pigment, isoindolinone Compound pigments, pyranthrone compound pigments, isoviolanthrone compound pigments, or mixtures thereof.
　本発明における無機顔料としては、特に限定されないが、一例を挙げると、金属化合物等が挙げられる。特に限定されないが、ベンガラ、黒色酸化鉄、黄酸化鉄系化合物、白色顔料としての酸化チタンや酸化亜鉛、紺青、群青、酸化クロム、酸化マグネシウムや酸化アルミニウム、酸化カルシウム、酸化ジルコニウムや、カドミウムや亜鉛の硫化物、その他の無機着色顔料及び無機化合物全般など全ての金属化合物が挙げられる。 The inorganic pigment in the present invention is not particularly limited, and examples thereof include metal compounds. Although not particularly limited, bengara, black iron oxide, yellow iron oxide compounds, titanium oxide and zinc oxide as white pigments, bitumen, ultramarine, chromium oxide, magnesium oxide and aluminum oxide, calcium oxide, zirconium oxide, cadmium and zinc All metal compounds such as sulfides, other inorganic color pigments and inorganic compounds in general.
　前記微粒子原料を溶解するための溶媒としては、例えば水や有機溶媒、またはそれらの複数からなる混合溶媒が挙げられる。前記水としては、水道水やイオン交換水、純水や超純水、ＲＯ水などが挙げられ、有機溶媒としては、アルコール系溶媒、アミド系溶媒、ケトン系溶媒、エーテル系溶媒、芳香族系溶媒、二硫化炭素、脂肪族系溶媒、ニトリル系溶媒、スルホキシド系溶媒、ハロゲン系溶媒、エステル系溶媒、イオン性液体、カルボン酸化合物、スルホン酸化合物などが挙げられる。前記の溶媒はそれぞれ単独で使用しても良く、または複数以上を混合して使用しても良い。 Examples of the solvent for dissolving the fine particle raw material include water, an organic solvent, or a mixed solvent composed of a plurality of them. Examples of the water include tap water, ion-exchanged water, pure water, ultrapure water, and RO water. Examples of the organic solvent include alcohol solvents, amide solvents, ketone solvents, ether solvents, aromatic solvents. Examples include solvents, carbon disulfide, aliphatic solvents, nitrile solvents, sulfoxide solvents, halogen solvents, ester solvents, ionic liquids, carboxylic acid compounds, and sulfonic acid compounds. Each of the above solvents may be used alone or in combination of two or more.
　また、前記溶媒に塩基性物質または酸性物質を混合または溶解しても実施できる。塩基性物質としては、水酸化ナトリウムや水酸化カリウムなどの金属水酸化物、ナトリウムメトキシドやナトリウムイソプロポキシドのような金属アルコキシド、さらにトリエチルアミンや２－ジエチルアミノエタノール、ジエチルアミンなどのアミン系化合物などが挙げられる。酸性物質としては、王水、塩酸、硝酸、発煙硝酸、硫酸、発煙硫酸などの無機酸や、ギ酸、酢酸、クロロ酢酸、ジクロロ酢酸、シュウ酸、トリフルオロ酢酸、トリクロロ酢酸などの有機酸が挙げられる。これらの塩基性物質または酸性物質は、前記の通り各種溶媒と混合しても実施できるし、それぞれ単独でも使用できる。 Further, the present invention can also be carried out by mixing or dissolving a basic substance or an acidic substance in the solvent. Examples of basic substances include metal hydroxides such as sodium hydroxide and potassium hydroxide, metal alkoxides such as sodium methoxide and sodium isopropoxide, and amine compounds such as triethylamine, 2-diethylaminoethanol and diethylamine. Can be mentioned. Examples of acidic substances include inorganic acids such as aqua regia, hydrochloric acid, nitric acid, fuming nitric acid, sulfuric acid and fuming sulfuric acid, and organic acids such as formic acid, acetic acid, chloroacetic acid, dichloroacetic acid, oxalic acid, trifluoroacetic acid and trichloroacetic acid. It is done. These basic substances or acidic substances can be carried out by mixing with various solvents as described above, or can be used alone.
　その他、前記溶媒に酸化剤や還元剤を混合または溶解しても実施できる。酸化剤としては、特に限定されないが、硝酸塩や、次亜塩素酸塩、過マンガン酸塩や過酸化物が挙げられる。還元剤としては、水素化アルミニウムリチウムや水素化ホウ素ナトリウム、ヒドラジンやヒドラジンの水和物、亜流酸塩、金属のイオン特に遷移金属のイオン（鉄イオンやチタンイオンなど）などが挙げられる。 In addition, it can also be carried out by mixing or dissolving an oxidizing agent or a reducing agent in the solvent. Although it does not specifically limit as an oxidizing agent, Nitrate, hypochlorite, permanganate, and a peroxide are mentioned. Examples of the reducing agent include lithium aluminum hydride and sodium borohydride, hydrazine and hydrazine hydrate, sulfite, metal ions, particularly transition metal ions (iron ions, titanium ions, etc.).
　前記微粒子原料溶液と混合して前記微粒子原料溶液から微粒子原料を析出させるための析出溶媒としては、前記の溶媒と同様のものが使用できる。前記微粒子原料を溶解させるための溶媒と、析出させる溶媒とは、目的とする微粒子によって溶解するための溶媒と析出させるための溶媒を選択して実施できる。 As a precipitation solvent for mixing with the fine particle raw material solution and precipitating the fine particle raw material from the fine particle raw material solution, the same solvent as the above solvent can be used. The solvent for dissolving the fine particle raw material and the solvent for precipitation can be carried out by selecting a solvent for dissolving the target fine particles and a solvent for precipitation.
　本発明においては、前記微粒子原料溶液の調製について回転する攪拌翼を有する攪拌機を用いて行うことが好ましい。具体的には、少なくとも１種類の微粒子原料を溶媒に溶解させて微粒子原料溶液を得る際に、回転する攪拌翼を有する攪拌機を用いる。これによってこれまで微粒子原料溶液中における未溶解物が原因となる粗大粒子の発生を抑えることができることは当然ながら、２種以上の分子や元素を溶解する場合にも、より均一な溶解状態である微粒子原料溶液を迅速に作製することができる。
　前処理で単に微粒子原料を溶媒に溶解させるだけでは均一な溶解状態を得ることができないが、微粒子原料溶液の調製を回転する攪拌翼を有する攪拌機を用いて行うことにより、分子レベルでの均一な溶解状態もしくは分子分散状態をなした微粒子原料溶液を得ることができ、微粒子原料溶液の溶解状態やクラスター形成状態を向上させることができたものと発明者は推測している。実際、発明者は、試行錯誤を繰り返しながら攪拌機の諸条件を変更させて微粒子原料溶液を調製し、調製した微粒子原料溶液と析出溶媒とを、対向して配設された、接近・離反可能な、少なくとも一方が他方に対して相対的に回転する少なくとも２つの処理用面間に導入し、前記少なくとも２つの処理用面間に形成される薄膜流体中で混合して、微粒子を析出させる実験を行った結果、攪拌機の諸条件の変更による攪拌エネルギーの増減と微粒子の粒子径や結晶化度、結晶型との間に関係性が見られたことは、大きな驚きであった。ここで、攪拌機の諸条件として、攪拌機による攪拌時間、攪拌翼の周速度、微粒子原料溶液の温度のうち少なくとも１つを変化させることにより、攪拌エネルギーを増減させた。 In the present invention, the fine particle raw material solution is preferably prepared using a stirrer having a rotating stirring blade. Specifically, when at least one kind of fine particle raw material is dissolved in a solvent to obtain a fine particle raw material solution, a stirrer having a rotating stirring blade is used. As a matter of course, it is possible to suppress the generation of coarse particles caused by undissolved substances in the fine particle raw material solution so far, even when two or more kinds of molecules and elements are dissolved, it is a more uniform dissolved state. A fine particle raw material solution can be rapidly produced.
Although it is not possible to obtain a uniform dissolved state simply by dissolving the fine particle raw material in the solvent in the pretreatment, the preparation of the fine particle raw material solution is performed using a stirrer having a rotating agitating blade to obtain a uniform molecular level. The inventor presumes that a fine particle raw material solution in a dissolved state or a molecular dispersion state can be obtained, and that the dissolved state and the cluster formation state of the fine particle raw material solution can be improved. In fact, the inventor changed the various conditions of the stirrer while repeating trial and error to prepare a fine particle raw material solution, and the prepared fine particle raw material solution and the precipitation solvent are arranged to face each other and can be approached and separated. An experiment in which at least one is introduced between at least two processing surfaces rotating relative to the other and mixed in a thin film fluid formed between the at least two processing surfaces to precipitate fine particles. As a result, it was a great surprise that there was a relationship between the increase / decrease in stirring energy by changing various conditions of the stirrer and the particle size, crystallinity, and crystal type of the fine particles. Here, as various conditions of the stirrer, the stirring energy was increased or decreased by changing at least one of the stirring time by the stirrer, the peripheral speed of the stirring blade, and the temperature of the fine particle raw material solution.
　本発明の実施の形態としては種々のものを例示することができるが、一例を挙げると、アシッドペースティング法により微粒子を析出させる場合、前記攪拌機の諸条件の変更による攪拌エネルギーを増加させることにより、析出させた微粒子の粒子径に対する結晶化度の比率が上昇するように制御することができる。
　他の例としては、アシッドペースティング法により微粒子を析出させる場合、前記攪拌機の諸条件の変更による攪拌エネルギーを増加させることにより、析出させた微粒子の粒子径に対する特定結晶型の構成比率の比率が上昇するように制御することができる。
　また他の例としては、アルカリペースト法により微粒子を析出させる場合、前記攪拌機の諸条件の変更による攪拌エネルギーを増加させることにより、析出させた微粒子の粒子径に対する結晶化度の比率が上昇するように制御することができる。
　さらにまた他の例としては、アルカリペースト法により微粒子を析出させる場合、前記攪拌機の諸条件の変更による攪拌エネルギーを増加させることにより、析出させた微粒子の粒子径に対する特定結晶型の構成比率の比率が上昇するように制御することができる。 Various embodiments can be exemplified as embodiments of the present invention. For example, when fine particles are precipitated by the acid pasting method, the stirring energy is increased by changing the conditions of the stirrer. The ratio of crystallinity to the particle diameter of the precipitated fine particles can be controlled to increase.
As another example, when the fine particles are precipitated by the acid pasting method, the ratio of the composition ratio of the specific crystal type to the particle size of the precipitated fine particles is increased by increasing the stirring energy by changing the conditions of the stirrer. It can be controlled to rise.
As another example, when the fine particles are precipitated by the alkali paste method, the ratio of crystallinity to the particle diameter of the precipitated fine particles is increased by increasing the stirring energy by changing various conditions of the stirrer. Can be controlled.
As yet another example, when the fine particles are precipitated by the alkali paste method, the ratio of the composition ratio of the specific crystal type to the particle size of the precipitated fine particles is increased by increasing the stirring energy by changing the conditions of the stirrer. Can be controlled to rise.
　一般的な攪拌子を用いて長時間の攪拌混合を行うことは、微粒子原料に含まれる分子やイオンなどが部分的に分解するなどの問題があるため好ましくないが、本発明において回転する攪拌翼を有する攪拌機を用いた攪拌時間を限定するものではない。 It is not preferable to perform agitation and mixing for a long time using a general stirrer because of problems such as partial decomposition of molecules and ions contained in the fine particle raw material. The stirring time using the stirrer having the above is not limited.
　本発明における攪拌機は、回転する攪拌翼を有する攪拌機であれば特に限定されないが、一般的な回転する攪拌翼を有する攪拌機においては、撹拌翼の先端での周速度が１ｍ／ｓｅｃ以上であるものが高速回転であると言われている。また、攪拌の方法は特に限定されないが、各種せん断式、摩擦式、高圧ジェット式、超音波式などの攪拌機や溶解機、乳化機、分散機、ホモジナイザーなどを用いて実施することができる。一例としては、ウルトラタラックス（ＩＫＡ社製）、ＴＫホモミキサー（プライミクス株式会社製）、ＴＫホモミックラインフロー、フィルミックス（共にプライミクス株式会社製）などの連続式乳化機、クレアミックス（エム・テクニック株式会社製）、クレアミックスディゾルバー（エム・テクニック株式会社製）などのバッチ式若しくは連続両用乳化機が挙げられる。その他、超音波式のホモジナイザーや超音波洗浄機、高圧ホモジナイザーなどを用いて微粒子原料溶液を調製しても良い。 The stirrer in the present invention is not particularly limited as long as it is a stirrer having a rotating stirring blade, but in a general stirrer having a rotating stirring blade, the peripheral speed at the tip of the stirring blade is 1 m / sec or more. Is said to be high-speed rotation. Further, the stirring method is not particularly limited, but it can be carried out using various shearing type, friction type, high pressure jet type, ultrasonic type stirring machines, dissolving machines, emulsifying machines, dispersing machines, homogenizers and the like. Examples include continuous emulsifiers such as Ultra Turrax (manufactured by IKA), TK homomixer (manufactured by Primics), TK homomic line flow, fill mix (both by Primics), Claremix (M And batch-type or continuous-use emulsifiers such as Technic Co., Ltd. and Claremix Dissolver (M Technic Co., Ltd.). In addition, the fine particle raw material solution may be prepared using an ultrasonic homogenizer, an ultrasonic cleaner, a high-pressure homogenizer, or the like.
　次に、回転する攪拌翼を有する攪拌機は前述したとおり、種々の形態のものを使用することができるが、その一例を挙げれば、複数の吐出口が形成されたスクリーンを有する攪拌室と、この攪拌室内にて回転する攪拌翼とを備え、攪拌翼の先端がスクリーンの内面に対して微小間隔を保って回転するように構成された攪拌機を示すことができる。スクリーンと攪拌翼とは相対的に回転するものであればよく、スクリーンは攪拌翼の回転方向と逆方向に回転するものであってもよく、固定されて回転しないものであってもよい。
　この形態に係る攪拌機を図４及び図５を参照して、より詳しく説明する。
　この回転する攪拌翼を有する攪拌機は、図４に示すように、被処理流動体を収容する収容槽１０１内に、蓋体１０２を貫通して、挿入される。以下、図４及び図５においては、攪拌翼を羽根１０７とする。
　この回転する攪拌翼を有する攪拌機は、図５に示すように、撹拌室１０３と、この撹拌室１０３を支持する支持筒１０４とを備える。撹拌室１０３の内部には、羽根車１０５が収容されている。この羽根車１０５は回転軸１０６の先端に設けられており、回転軸１０６は支持筒１０４内部に配置されている。支持筒１０４及び攪拌室１０３に対して、回転軸１０６及び羽根車１０５は、逆方向に回転する。支持筒１０４及び回転軸１０６のそれぞれの基端は、別個の回転駆動手段（図示せず）に接続されている。
　撹拌室１０３は、支持筒１０４の先端に設けられたハウジング１２１と、ハウジング１２１の先端側に設けられたスクリーン１２２とを備える。ハウジング１２１に吸入口１２３が形成されており、スクリーン１２２に吐出口１２５が形成されている。羽根車１０５の回転によってこの吸入口１２３から被処理流動体が撹拌室１０３内へ導かれ、分散、溶解等処理の後、前記吐出口１２５から外部へ被処理流動体が吐出される。なお、吐出口１２５を吸入口とし、吸入口１２３を吐出口として実施してもよい。スクリーン１２２の内部と、ハウジング１２１の内部とを区画するために、仕切り１２４を設けることもできるが、設けずに実施することもできる。
　特に、羽根車１０５の羽根１０７の先端は、スクリーン１２２の内壁に微小な間隔を保って沿わされている。この微小な間隔は、約０．２～２ｍｍに設定されることが望ましく、この微小な間隙において被処理流動体に対して、大きなせん断力が加えられるとともに羽根車１０５の回転によって、被処理流動体に運動エネルギーが与えられ、羽根１０７の回転方向の前方では、被処理流動体の圧力が高まり、この高圧の被処理流動体が吐出口１２５を通過することによって、さらに加速され、断続ジェット流を形成しながらスクリーン１２２の外部へ吐出される。一方、羽根１０７の回転方向の後方では負圧となり、羽根１０７が吐出口１２５を通過した直後には吐出口１２５からスクリーン１２２の内部に被処理流動体が吸引される。この被処理流動体の正逆の流れによって被処理流動体同士の間にせん断力が生じることになる。
　上記の作用は、スクリーン１２２を有する撹拌室１０３と羽根車１０５とを相対的に回転させることよって達成される。具体的には、静止状態の撹拌室１０３の内部で攪拌翼である羽根１０７を回転させることによって得ることができる。また、前述の例のように、撹拌室１０３と羽根車１０５とを互いに逆方向に回転させることによって、吐出口１２５が羽根車１０５の回転方向と逆方向に回転させるものとして実施することもできる。これにより両者間の相対的な回転数を上げることができ、被処理流動体のせん断処理能力を、より高めることができる。
　本発明はこれに限定されるものではなく、吐出口１２５を有するスクリーン１２２を取り外して、吸入口１２３を有するハウジング１２１のみ設けて、これを回転させるようにしてもよい。スクリーン１２２を取り外すことで、被処理流動体にせん断力を与えず、キャビテーションコントロールを行いつつ短時間で被処理流動体の溶解をなすことができる。しかしながら、ハウジング１２１の先端側にスクリーン１２２を設けた方が、断続ジェット流が発生するため好ましい。羽根車１０５とスクリーン１２２とは、相対的に回転することによって、吐出口１２５を含むスクリーン１２２の内壁と羽根１０７の先端との間の微小な間隙において被処理流動体のせん断が行われると共に、吐出口１２５を通じて断続ジェット流としてスクリーン１２２の内側から外側に被処理流動体が吐出されるものである。微粒子原料溶液の調製に際し、微粒子原料の溶媒への溶解に断続ジェット流が有効に作用し、微粒子原料溶液が分子レベルの溶解状態もしくは分子分散状態をなしていると発明者は推測している。
　このように、撹拌室１０３に設けられた吸入口１２３及び吐出口１２５の一方或いは双方が回転するため、撹拌室１０３の外部の被処理流動体に対して、被処理流動体の吸入或いは吐出もしくはその双方の位置を順次変えていくことになり、循環から疎外された被処理流動体の発生を防ぐことができる。なお、攪拌室１０３を設けずに実施し、羽根車１０５のみをむき出しにして、回転させるようにしてもよい。
　被処理流動体の循環を収容槽１０１全領域に渡って確実に行うために、支持筒１０４の長手方向に沿って螺旋状に巻回する導入フィン１３１を設けてもよい。この導入フィン１３１が支持筒１０４と同体に回転することにより、収容槽１０１内上方に位置する被処理流動体が、支持筒１０４外周に沿って降下し、吸入口１２３へ導かれる。また、前記導入フィン１３１と逆方向に巻回される循環フィン１３２を設けることも可能である。この循環フィン１３２は、導入フィン１３１の外側に配置され、吐出口１２５から吐出された被処理流動体を収容槽１０１の上方へ循環させる。
　なお、図４及び図５に示された撹拌機は、上述のクレアミックス（エム・テクニック株式会社製）として製品化されている。また、上述のクレアミックス（エム・テクニック株式会社製）からスクリーンを取り外したクレアミックスディゾルバー（エム・テクニック株式会社製）を用いてもよい。
　前述のように、一般的な攪拌機では、撹拌翼の先端での周速度が１ｍ／ｓｅｃ以上であるものが高速回転であると言われているが、前記のクレアミックスやクレアミックスディゾルバーにおいて、良好な攪拌状態を得るには、撹拌翼の先端での周速度が３１．４２ｍ／ｓｅｃ以上の高速回転を行うことが望ましい。 Next, as described above, the stirrer having a rotating stirring blade can be used in various forms. For example, a stirring chamber having a screen having a plurality of discharge ports, A stirrer that includes a stirring blade that rotates in the stirring chamber and that is configured so that the tip of the stirring blade rotates with a small distance from the inner surface of the screen can be shown. The screen and the stirring blade are only required to rotate relatively, and the screen may be rotated in the direction opposite to the rotation direction of the stirring blade, or may be fixed and not rotated.
The stirrer according to this embodiment will be described in more detail with reference to FIG. 4 and FIG.
As shown in FIG. 4, the stirrer having the rotating stirring blade is inserted through the lid 102 into the storage tank 101 that stores the fluid to be processed. Hereinafter, in FIG. 4 and FIG.
As shown in FIG. 5, the stirrer having the rotating stirring blade includes a stirring chamber 103 and a support cylinder 104 that supports the stirring chamber 103. An impeller 105 is accommodated in the stirring chamber 103. The impeller 105 is provided at the tip of the rotation shaft 106, and the rotation shaft 106 is disposed inside the support cylinder 104. The rotating shaft 106 and the impeller 105 rotate in the opposite direction with respect to the support cylinder 104 and the stirring chamber 103. The base ends of the support cylinder 104 and the rotation shaft 106 are connected to separate rotation driving means (not shown).
The stirring chamber 103 includes a housing 121 provided at the front end of the support cylinder 104 and a screen 122 provided at the front end side of the housing 121. A suction port 123 is formed in the housing 121, and a discharge port 125 is formed in the screen 122. The fluid to be processed is guided from the suction port 123 into the stirring chamber 103 by the rotation of the impeller 105, and after the processing such as dispersion and dissolution, the fluid to be processed is discharged from the discharge port 125 to the outside. The discharge port 125 may be used as the suction port, and the suction port 123 may be used as the discharge port. In order to partition the inside of the screen 122 and the inside of the housing 121, the partition 124 can be provided, but can also be implemented without providing it.
In particular, the tip of the blade 107 of the impeller 105 runs along the inner wall of the screen 122 with a small interval. This minute interval is preferably set to about 0.2 to 2 mm, and a large shearing force is applied to the fluid to be treated in this minute gap, and the fluid to be treated is caused by the rotation of the impeller 105. Kinetic energy is given to the body, and the pressure of the fluid to be treated is increased in front of the rotation direction of the blades 107. This high-pressure fluid to be treated passes through the discharge port 125, and is further accelerated. Are discharged to the outside of the screen 122. On the other hand, the pressure is negative behind the rotation direction of the blade 107, and the fluid to be processed is sucked into the screen 122 from the discharge port 125 immediately after the blade 107 passes through the discharge port 125. A shear force is generated between the fluids to be treated due to the reverse flow of the fluids to be treated.
The above action is achieved by relatively rotating the stirring chamber 103 having the screen 122 and the impeller 105. Specifically, it can be obtained by rotating the blade 107 as a stirring blade inside the stirring chamber 103 in a stationary state. Further, as in the above-described example, the discharge port 125 can be rotated in the direction opposite to the rotation direction of the impeller 105 by rotating the stirring chamber 103 and the impeller 105 in the opposite directions. . Thereby, the relative rotation speed between both can be raised, and the shearing ability of the fluid to be treated can be further increased.
The present invention is not limited to this, and the screen 122 having the discharge port 125 may be removed, and only the housing 121 having the suction port 123 may be provided and rotated. By removing the screen 122, the fluid to be treated can be dissolved in a short time while performing cavitation control without applying a shearing force to the fluid to be treated. However, it is preferable to provide the screen 122 on the front end side of the housing 121 because an intermittent jet flow is generated. As the impeller 105 and the screen 122 rotate relatively, the fluid to be processed is sheared in a minute gap between the inner wall of the screen 122 including the discharge port 125 and the tip of the blade 107, and The fluid to be processed is discharged from the inside to the outside of the screen 122 as an intermittent jet flow through the discharge port 125. In preparing the fine particle raw material solution, the inventor presumes that the intermittent jet flow effectively acts on the dissolution of the fine particle raw material in the solvent, and the fine particle raw material solution has a molecular level dissolved state or molecular dispersed state.
As described above, one or both of the suction port 123 and the discharge port 125 provided in the stirring chamber 103 rotate, so that the fluid to be processed is sucked or discharged or discharged from the fluid to be processed outside the stirring chamber 103. Both the positions are sequentially changed, and the generation of the fluid to be treated that is excluded from the circulation can be prevented. Alternatively, the agitation chamber 103 may be omitted, and only the impeller 105 may be exposed and rotated.
In order to reliably circulate the fluid to be processed over the entire area of the storage tank 101, an introduction fin 131 that is spirally wound along the longitudinal direction of the support cylinder 104 may be provided. When the introduction fin 131 rotates in the same body as the support cylinder 104, the fluid to be processed located in the upper part of the storage tank 101 descends along the outer periphery of the support cylinder 104 and is guided to the suction port 123. It is also possible to provide a circulation fin 132 wound in the opposite direction to the introduction fin 131. The circulation fins 132 are arranged outside the introduction fins 131 and circulate the fluid to be processed discharged from the discharge ports 125 upward of the storage tank 101.
In addition, the stirrer shown by FIG.4 and FIG.5 is commercialized as the above-mentioned Clare mix (made by M technique Co., Ltd.). Moreover, you may use the Clare mix dissolver (made by M technique Co., Ltd.) which removed the screen from the above-mentioned Clare mix (made by M technique Co., Ltd.).
As described above, in a general stirrer, it is said that the peripheral speed at the tip of the stirring blade is 1 m / sec or more is said to be high-speed rotation, but in the above-mentioned Clare mix and Clare mix dissolver, it is good. In order to obtain a stable stirring state, it is desirable to perform high-speed rotation with a peripheral speed of 31.42 m / sec or more at the tip of the stirring blade.
　羽根車１０５の羽根１０７は、横断面（回転軸１０６の軸方向に直交する断面）において、羽根車１０５の中心から放射状に一定の幅で直線状に伸びるものであってもよく、外側に向かうに従って漸次幅が広くなるものであってもよく、湾曲しながら外側に伸びるものであってもよい。また、回転軸１０６の軸方向においては、これらの羽根１０７は、回転軸１０６の回転軸を含む平面に沿って、直線状に伸びるものであってもよく、スパイラル状など、上下方向に湾曲して伸びるものであってもよい。
　また、羽根車１０５の羽根１０７の最大外径は、実施態様に応じて適宜設定することができる。
　また、吐出口１２５は、回転軸１０６の軸方向に（図の例では上下方向）に直線状に伸びるものを示したが、スパイラル状など、湾曲して伸びるものであってもよい。また、吐出口１２５の形状は、必ずしも細長い空間である必要はなく、多角形や円形や楕円形などであってもよい。また、周方向において、吐出口１２５は等間隔に複数個が形成されているが、間隔をずらして形成することもでき、複数種類の形状や大きさの吐出口１２５を設けることを妨げるものでもない。 The blades 107 of the impeller 105 may extend linearly from the center of the impeller 105 with a certain width in a cross section (cross section orthogonal to the axial direction of the rotating shaft 106), and go outward. Accordingly, the width may be gradually increased, or may be extended outward while being curved. Further, in the axial direction of the rotating shaft 106, these blades 107 may extend linearly along a plane including the rotating shaft of the rotating shaft 106, and bend in a vertical direction such as a spiral shape. It may extend.
Further, the maximum outer diameter of the blade 107 of the impeller 105 can be appropriately set according to the embodiment.
In addition, although the discharge port 125 is illustrated as extending linearly in the axial direction of the rotation shaft 106 (vertical direction in the example in the figure), it may be curved and extended such as a spiral shape. Further, the shape of the discharge port 125 is not necessarily an elongated space, and may be a polygon, a circle, an ellipse, or the like. In the circumferential direction, a plurality of discharge ports 125 are formed at equal intervals. However, the discharge ports 125 may be formed at different intervals, and may prevent the discharge ports 125 having a plurality of types and sizes from being provided. Absent.
　また、本発明は、前記のクレアミックスやクレアミックスディゾルバーを用いるものに限定されるものではなく、一般的な攪拌翼を有する撹拌機を用いて実施することもできる。その際、微粒子原料を溶媒に溶解する際の攪拌翼の周速度は、特に限定されないが、１ｍ／ｓｅｃ以上である事が好ましい。溶媒の粘度や温度、または溶解する微粒子原料の濃度によって適宜使い分けることができる。
　本発明において、攪拌翼の周速度とは、攪拌翼の最大外径部における移動速度を意味し、具体的には、以下の式より算出される。
　周速度ｖ［ｍ／ｓ］＝ｒω＝２×π×ｒ［ｍ］×ｆ［ｒｐｍ］／６０
　ここで、ｒは攪拌翼の最大半径、ωは角速度、ｆは攪拌翼の単位時間当たりの回転数、πは円周率を示す。 Moreover, this invention is not limited to what uses the said Clare mix and a Clare mix dissolver, It can also implement using the stirrer which has a general stirring blade. At that time, the peripheral speed of the stirring blade when dissolving the fine particle raw material in the solvent is not particularly limited, but is preferably 1 m / sec or more. It can be properly used depending on the viscosity and temperature of the solvent or the concentration of the fine particle raw material to be dissolved.
In the present invention, the peripheral speed of the stirring blade means a moving speed in the maximum outer diameter portion of the stirring blade, and is specifically calculated from the following equation.
Peripheral speed v [m / s] = rω = 2 × π × r [m] × f [rpm] / 60
Here, r is the maximum radius of the stirring blade, ω is the angular velocity, f is the rotational speed of the stirring blade per unit time, and π is the circumference.
　前記の説明においては、同一の攪拌機を用いてその諸条件（攪拌時間、攪拌翼の周速度、微粒子原料溶液の温度）を変化させて攪拌エネルギーを増減させることについて記載したが、分子レベルでの溶解状態もしくは分子分散状態をなす微粒子原料溶液を得、微粒子原料溶液と析出溶媒との薄膜流体中の混合により析出させた微粒子の性状／特性を制御することができれば、複数の装置を用いて前記の諸条件を変化させて攪拌エネルギーを増減させてもよい。　 In the above description, it is described that the same energy is used to change the various conditions (stirring time, peripheral speed of the stirring blade, temperature of the fine particle raw material solution) to increase or decrease the stirring energy. If a fine particle raw material solution in a dissolved state or a molecular dispersion state is obtained and the properties / characteristics of the fine particles deposited by mixing the fine particle raw material solution and the precipitation solvent in the thin film fluid can be controlled, a plurality of devices may be used. The stirring energy may be increased or decreased by changing these conditions. *
　また、分子レベルでの溶解状態もしくは分子分散状態をなす微粒子原料溶液を得ることができれば、攪拌機のその他の条件を変化させて実施してもよい。例えば、図４及び図５の羽根車１０５の羽根１０７の形状とスクリーン１２２の吐出口１２５の形状との組み合わせを変更することによっても、分子レベルでの溶解状態もしくは分子分散状態をなす微粒子原料溶液を得る可能性がある。より詳しくは、（Ａ）回転軸１０６から遠ざかるに従って回転軸１０６の回転方向と逆方向に湾曲して伸びる羽根１０７又は（Ｂ）回転軸の半径方向に直線状に伸びた羽根１０７、（Ｃ）１ｍｍ幅の吐出口１２５が２４本のスクリーン１２２又は（Ｄ）２ｍｍ幅の吐出口１２５が２４本のスクリーン１２２をそれぞれ用い、その組み合わせを変更することによっても、分子レベルでの溶解状態もしくは分子分散状態をなす微粒子原料溶液を得、その後、微粒子原料溶液と析出溶媒との薄膜流体中の混合により析出させた微粒子の性状／特性を制御することができる。
　前記の組み合わせは、微粒子原料溶液が高濃度の場合、（Ａ）（Ｄ）の組み合わせを用いると、溶液の攪拌効果が高まり、分子、イオンの溶解性や分散性を向上することができると考える。 Moreover, as long as the fine particle raw material solution in a dissolved state or molecular dispersed state at the molecular level can be obtained, the other conditions of the stirrer may be changed. For example, by changing the combination of the shape of the blade 107 of the impeller 105 of FIG. 4 and FIG. 5 and the shape of the discharge port 125 of the screen 122, the fine particle raw material solution that is dissolved or dispersed in the molecular level. You might get. More specifically, (A) a blade 107 that curves and extends in a direction opposite to the rotation direction of the rotation shaft 106 as it moves away from the rotation shaft 106, or (B) a blade 107 that extends linearly in the radial direction of the rotation shaft, (C) The 1 mm wide discharge port 125 has 24 screens 122 or (D) the 2 mm wide discharge port 125 has 24 screens 122, and the dissolved state or molecular dispersion at the molecular level can be changed by changing the combination. The properties / characteristics of the fine particles deposited can be controlled by obtaining the fine particle raw material solution in a state and then mixing the fine particle raw material solution and the precipitation solvent in the thin film fluid.
In the case of the above-mentioned combination, when the fine particle raw material solution has a high concentration, if the combination of (A) and (D) is used, the stirring effect of the solution is enhanced and the solubility and dispersibility of molecules and ions can be improved. .
　以下、図面を用いて前記の、対向して配設された、接近・離反可能な、少なくとも一方が他方に対して相対的に回転する少なくとも２つの処理用面間において微粒子を析出させる装置の実施の形態について説明する。 Hereinafter, implementation of the apparatus for depositing fine particles between at least two processing surfaces disposed opposite to each other and capable of approaching / separating, at least one rotating relative to the other, with reference to the drawings. Will be described.
　図１～図３に示す流体処理装置は、特許文献３に記載の装置と同様であり、接近・離反可能な少なくとも一方が他方に対して相対的に回転する処理用部における処理用面の間で被処理物を処理するものであって、被処理流動体のうちの第１の被処理流動体である第１流体を処理用面間に導入し、前記流体を導入した流路とは独立し、処理用面間に通じる開口部を備えた別の流路から被処理流動体のうちの第２の被処理流動体である第２流体を処理用面間に導入して処理用面間で前記第１流体と第２流体を混合・攪拌して処理を行う装置である。なお、図１においてＵは上方を、Ｓは下方をそれぞれ示しているが、本発明において上下前後左右は相対的な位置関係を示すに止まり、絶対的な位置を特定するものではない。図２（Ａ）、図３（Ｂ）においてＲは回転方向を示している。図３（Ｂ）においてＣは遠心力方向（半径方向）を示している。 The fluid processing apparatus shown in FIGS. 1 to 3 is the same as the apparatus described in Patent Document 3, and between the processing surfaces in the processing unit in which at least one of which can be approached / separated rotates relative to the other. The first fluid, which is the first fluid to be treated, of the fluids to be treated is introduced between the processing surfaces and is independent of the flow path into which the fluid is introduced. Then, the second fluid, which is the second fluid to be processed, is introduced between the processing surfaces from another flow path having an opening communicating between the processing surfaces. In the apparatus, the first fluid and the second fluid are mixed and stirred. In FIG. 1, U indicates the upper side and S indicates the lower side. However, in the present invention, the upper, lower, front, rear, left and right only indicate a relative positional relationship, and do not specify an absolute position. 2A and 3B, R indicates the direction of rotation. In FIG. 3B, C indicates the centrifugal force direction (radial direction).
　この装置は、被処理流動体として少なくとも２種類の流体を用いるものであり、そのうちで少なくとも１種類の流体については被処理物を少なくとも１種類含むものであり、接近・離反可能に互いに対向して配設され、少なくとも一方が他方に対して回転する処理用面を備え、これらの処理用面の間で前記の各流体を合流させて薄膜流体とするものであり、当該薄膜流体中において前記の被処理物を処理する装置である。この装置は、上述のとおり、複数の被処理流動体を処理することができるが、単一の被処理流動体を処理することもできる。 This apparatus uses at least two kinds of fluids as a fluid to be treated, and at least one kind of fluid includes at least one kind of an object to be treated and is opposed to each other so as to be able to approach and separate. A processing surface that is disposed and at least one of which rotates relative to the other, and combines the fluids between the processing surfaces to form a thin film fluid. An apparatus for processing an object to be processed. As described above, this apparatus can process a plurality of fluids to be processed, but can also process a single fluid to be processed.
　この流体処理装置は、対向する第１及び第２の、２つの処理用部１０，２０を備え、少なくとも一方の処理用部が回転する。両処理用部１０，２０の対向する面が、夫々処理用面となる。第１処理用部１０は第１処理用面１を備え、第２処理用部２０は第２処理用面２を備える。 This fluid processing apparatus includes first and second processing units 10 and 20 that face each other, and at least one of the processing units rotates. The opposing surfaces of both processing parts 10 and 20 are processing surfaces. The first processing unit 10 includes a first processing surface 1, and the second processing unit 20 includes a second processing surface 2.
　両処理用面１，２は、被処理流動体の流路に接続され、被処理流動体の流路の一部を構成する。この両処理用面１，２間の間隔は、適宜変更して実施することができるが、通常は、１ｍｍ以下、例えば０．１μｍから５０μｍ程度の微小間隔に調整される。これによって、この両処理用面１，２間を通過する被処理流動体は、両処理用面１，２によって強制された強制薄膜流体となる。 Both the processing surfaces 1 and 2 are connected to the flow path of the fluid to be processed and constitute a part of the flow path of the fluid to be processed. The distance between the processing surfaces 1 and 2 can be changed as appropriate, but is usually adjusted to 1 mm or less, for example, a minute distance of about 0.1 μm to 50 μm. As a result, the fluid to be processed that passes between the processing surfaces 1 and 2 becomes a forced thin film fluid forced by the processing surfaces 1 and 2.
　この装置を用いて複数の被処理流動体を処理する場合、この装置は、第１の被処理流動体の流路に接続され、当該第１被処理流動体の流路の一部を形成すると共に、第１被処理流動体とは別の、第２被処理流動体の流路の一部を形成する。そして、この装置は、両流路を合流させて、処理用面１，２間において、両被処理流動体を混合し、反応させるなどの流体の処理を行なう。なお、ここで「処理」とは、被処理物が反応する形態に限らず、反応を伴わずに混合・分散のみがなされる形態も含む。 When a plurality of fluids to be processed are processed using this apparatus, the apparatus is connected to the flow path of the first fluid to be processed and forms a part of the flow path of the first fluid to be processed. At the same time, a part of the flow path of the second fluid to be treated is formed separately from the first fluid to be treated. And this apparatus performs processing of fluid, such as making both flow paths merge and mixing both the to-be-processed fluids between the processing surfaces 1 and 2, and making it react. Here, “treatment” is not limited to a form in which the object to be treated reacts, but also includes a form in which only mixing and dispersion are performed without any reaction.
　具体的に説明すると、前記の第１処理用部１０を保持する第１ホルダ１１と、第２処理用部２０を保持する第２ホルダ２１と、接面圧付与機構と、回転駆動機構と、第１導入部ｄ１と、第２導入部ｄ２と、流体圧付与機構ｐとを備える。 Specifically, the first holder 11 that holds the first processing portion 10, the second holder 21 that holds the second processing portion 20, a contact pressure application mechanism, a rotation drive mechanism, A first introduction part d1, a second introduction part d2, and a fluid pressure imparting mechanism p are provided.
　図２（Ａ）へ示す通り、この実施の形態において、第１処理用部１０は、環状体であり、より詳しくはリング状のディスクである。また、第２処理用部２０もリング状のディスクである。第１、第２処理用部１０、２０の材質は、金属の他、セラミックや焼結金属、耐磨耗鋼、サファイア、その他金属に硬化処理を施したものや、硬質材をライニングやコーティング、メッキなどを施工したものを採用することができる。この実施の形態において、両処理用部１０，２０は、互いに対向する第１、第２の処理用面１、２の少なくとも一部が鏡面研磨されている。
　この鏡面研磨の面粗度は、特に限定されないが、好ましくはＲａ０．０１～１．０μｍ、より好ましくはＲａ０．０３～０．３μｍとする。 As shown in FIG. 2A, in this embodiment, the first processing portion 10 is an annular body, more specifically, a ring-shaped disk. The second processing unit 20 is also a ring-shaped disk. The first and second processing parts 10 and 20 are made of metal, ceramic, sintered metal, wear-resistant steel, sapphire, other metals subjected to hardening treatment, hard material lining or coating, It is possible to adopt a material with plating applied. In this embodiment, at least a part of the first and second processing surfaces 1 and 2 facing each other is mirror-polished in the processing units 10 and 20.
The surface roughness of this mirror polishing is not particularly limited, but is preferably Ra 0.01 to 1.0 μm, more preferably Ra 0.03 to 0.3 μm.
　少なくとも一方のホルダは、電動機などの回転駆動機構（図示せず）にて、他方のホルダに対して相対的に回転することができる。図１の５０は、回転駆動機構の回転軸を示しており、この例では、この回転軸５０に取り付けられた第１ホルダ１１が回転し、この第１ホルダ１１に支持された第１処理用部１０が第２処理用部２０に対して回転する。もちろん、第２処理用部２０を回転させるようにしてもよく、双方を回転させるようにしてもよい。また、この例では、第１、第２ホルダ１１、２１を固定しておき、この第１、第２ホルダ１１、２１に対して第１、第２処理用部１０、２０が回転するようにしてもよい。 At least one of the holders can be rotated relative to the other holder by a rotational drive mechanism (not shown) such as an electric motor. Reference numeral 50 in FIG. 1 denotes a rotation shaft of the rotation drive mechanism. In this example, the first holder 11 attached to the rotation shaft 50 rotates and is used for the first processing supported by the first holder 11. The unit 10 rotates with respect to the second processing unit 20. Of course, the second processing unit 20 may be rotated, or both may be rotated. In this example, the first and second holders 11 and 21 are fixed, and the first and second processing parts 10 and 20 are rotated with respect to the first and second holders 11 and 21. May be.
　第１処理用部１０と第２処理用部２０とは、少なくとも何れか一方が、少なくとも何れか他方に、接近・離反可能となっており、両処理用面１，２は、接近・離反できる。 At least one of the first processing unit 10 and the second processing unit 20 can be approached / separated from at least either one, and both processing surfaces 1 and 2 can be approached / separated. .
　この実施の形態では、第１処理用部１０に対して、第２処理用部２０が接近・離反するもので、第２ホルダ２１に設けられた収容部４１に、第２処理用部２０が出没可能に収容されている。但し、これとは、逆に、第１処理用部１０が、第２処理用部２０に対して接近・離反するものであってもよく、両処理用部１０，２０が互いに接近・離反するものであってもよい。 In this embodiment, the second processing unit 20 approaches and separates from the first processing unit 10, and the second processing unit 20 is disposed in the storage unit 41 provided in the second holder 21. It is housed in a hauntable manner. However, conversely, the first processing unit 10 may approach or separate from the second processing unit 20, and both the processing units 10 and 20 may approach or separate from each other. It may be a thing.
　この収容部４１は、第２処理用部２０の、主として処理用面２側と反対側の部位を収容する凹部であり、平面視において、円を呈する、即ち環状に形成された、溝である。この収容部４１は、第２処理用部２０を回転させ得る十分なクリアランスを持って、第２処理用部２０を収容する。なお、第２処理用部２０は軸方向に平行移動のみが可能なように配置してもよいが、前記クリアランスを大きくすることにより、第２処理用部２０は、収容部４１に対して、処理用部２０の中心線を、前記収容部４１の軸方向と平行の関係を崩すように傾斜して変位できるようにしてもよく、さらに、第２処理用部２０の中心線と収容部４１の中心線とが半径方向にずれるように変位できるようにしてもよい。
　このように、３次元的に変位可能に保持するフローティング機構によって、第２処理用部２０を保持することが望ましい。 The accommodating portion 41 is a recess that mainly accommodates a portion of the second processing portion 20 on the side opposite to the processing surface 2 side, and is a groove that has a circular shape, that is, is formed in an annular shape in plan view. . The accommodating portion 41 accommodates the second processing portion 20 with a sufficient clearance that allows the second processing portion 20 to rotate. The second processing unit 20 may be arranged so that only the parallel movement is possible in the axial direction, but by increasing the clearance, the second processing unit 20 is The center line of the processing unit 20 may be displaced by being inclined so as to break the relationship parallel to the axial direction of the storage unit 41. Furthermore, the center line of the second processing unit 20 and the storage unit 41 may be displaced. The center line may be displaced so as to deviate in the radial direction.
As described above, it is desirable to hold the second processing unit 20 by the floating mechanism that holds the three-dimensionally displaceably.
　前記の被処理流動体は、各種のポンプや位置エネルギーなどによって構成される流体圧付与機構ｐによって圧力が付与された状態で、第１導入部ｄ１と、第２導入部ｄ２から両処理用面１、２間に導入される。この実施の形態において、第１導入部ｄ１は、環状の第２ホルダ２１の中央に設けられた通路であり、その一端が、環状の両処理用部１０、２０の内側から、両処理用面１、２間に導入される。第２導入部ｄ２は、第１の被処理流動体と反応させる第２の被処理流動体を処理用面１，２へ供給する。この実施の形態において、第２導入部ｄ２は、第２処理用部２０の内部に設けられた通路であり、その一端が、第２処理用面２にて開口する。流体圧付与機構ｐにより加圧された第１の被処理流動体は、第１導入部ｄ１から、両処理用部１０，２０の内側の空間に導入され、第１処理用面１と第２処理用面２との間を通り、両処理用部１０，２０の外側に通り抜けようとする。これらの処理用面１，２間において、第２導入部ｄ２から流体圧付与機構ｐにより加圧された第２の被処理流動体が供給され、第１の被処理流動体と合流し、混合、攪拌、乳化、分散、反応、晶出、晶析、析出などの種々の流体処理がなされ、両処理用面１，２から、両処理用部１０，２０の外側に排出される。なお、減圧ポンプにより両処理用部１０，２０の外側の環境を負圧にすることもできる。 The above-described fluid to be treated is subjected to both treatment surfaces from the first introduction part d1 and the second introduction part d2 in a state where pressure is applied by a fluid pressure application mechanism p configured by various pumps and potential energy. It is introduced between 1 and 2. In this embodiment, the first introduction part d1 is a passage provided in the center of the annular second holder 21, and one end of the first introduction part d1 is formed on both processing surfaces from the inside of the annular processing parts 10, 20. It is introduced between 1 and 2. The second introduction part d2 supplies the second processing fluid to be reacted with the first processing fluid to the processing surfaces 1 and 2. In this embodiment, the second introduction part d <b> 2 is a passage provided inside the second processing part 20, and one end thereof opens at the second processing surface 2. The first fluid to be processed that has been pressurized by the fluid pressure imparting mechanism p is introduced from the first introduction part d1 into the space inside the processing parts 10 and 20, and the first processing surface 1 and the second processing surface 2 are supplied. It passes between the processing surfaces 2 and tries to pass outside the processing portions 10 and 20. Between these processing surfaces 1 and 2, the second fluid to be treated pressurized by the fluid pressure applying mechanism p is supplied from the second introduction part d 2, merged with the first fluid to be treated, and mixed. Various fluid treatments such as stirring, emulsification, dispersion, reaction, crystallization, crystallization, and precipitation are performed and discharged from both treatment surfaces 1 and 2 to the outside of both treatment portions 10 and 20. In addition, the environment outside both processing parts 10 and 20 can also be made into a negative pressure with a decompression pump.
　前記の接面圧付与機構は、第１処理用面１と第２処理用面２とを接近させる方向に作用させる力を、処理用部に付与する。この実施の形態では、接面圧付与機構は、第２ホルダ２１に設けられ、第２処理用部２０を第１処理用部１０に向けて付勢する。 The contact surface pressure applying mechanism applies to the processing portion a force that causes the first processing surface 1 and the second processing surface 2 to approach each other. In this embodiment, the contact pressure applying mechanism is provided in the second holder 21 and biases the second processing portion 20 toward the first processing portion 10.
　前記の接面圧付与機構は、第１処理用部１０の第１処理用面１と第２処理用部２０の第２処理用面２とが接近する方向に押す力（以下、接面圧力という）を発生させるための機構である。この接面圧力と、流体圧力などの両処理用面１、２間を離反させる力との均衡によって、ｎｍ単位ないしμｍ単位の微小な膜厚を有する薄膜流体を発生させる。言い換えれば、前記力の均衡によって、両処理用面１、２間の間隔を所定の微小間隔に保つ。 The contact surface pressure applying mechanism is a force that pushes in a direction in which the first processing surface 1 of the first processing unit 10 and the second processing surface 2 of the second processing unit 20 approach (hereinafter referred to as contact pressure). It is a mechanism for generating. A thin film fluid having a minute film thickness of nm to μm is generated by the balance between the contact pressure and the force for separating the processing surfaces 1 and 2 such as fluid pressure. In other words, the distance between the processing surfaces 1 and 2 is kept at a predetermined minute distance by the balance of the forces.
　図１に示す実施の形態において、接面圧付与機構は、前記の収容部４１と第２処理用部２０との間に配位される。具体的には、第２処理用部２０を第１処理用部１０に近づく方向に付勢するスプリング４３と、空気や油などの付勢用流体を導入する付勢用流体導入部４４とにて構成され、スプリング４３と前記付勢用流体の流体圧力とによって、前記の接面圧力を付与する。このスプリング４３と前記付勢用流体の流体圧力とは、いずれか一方が付与されるものであればよく、磁力や重力などの他の力であってもよい。この接面圧付与機構の付勢に抗して、流体圧付与機構ｐにより加圧された被処理流動体の圧力や粘性などによって生じる離反力によって、第２処理用部２０は、第１処理用部１０から遠ざかり、両処理用面間に微小な間隔を開ける。このように、この接面圧力と離反力とのバランスによって、第１処理用面１と第２処理用面２とは、μｍ単位の精度で設定され、両処理用面１，２間の微小間隔の設定がなされる。前記離反力としては、被処理流動体の流体圧や粘性と、処理用部の回転による遠心力と、付勢用流体導入部４４に負圧を掛けた場合の当該負圧、スプリング４３を引っ張りスプリングとした場合のバネの力などを挙げることができる。この接面圧付与機構は、第２処理用部２０ではなく、第１処理用部１０に設けてもよく、双方に設けてもよい。 In the embodiment shown in FIG. 1, the contact surface pressure applying mechanism is arranged between the accommodating portion 41 and the second processing portion 20. Specifically, a spring 43 that biases the second processing portion 20 in a direction approaching the first processing portion 10 and a biasing fluid introduction portion 44 that introduces a biasing fluid such as air or oil. The contact surface pressure is applied by the spring 43 and the fluid pressure of the biasing fluid. Any one of the spring 43 and the fluid pressure of the urging fluid may be applied, and other force such as magnetic force or gravity may be used. The second processing unit 20 causes the first treatment by the separation force generated by the pressure or viscosity of the fluid to be treated which is pressurized by the fluid pressure imparting mechanism p against the bias of the contact surface pressure imparting mechanism. Move away from the working part 10 and leave a minute gap between the processing surfaces. As described above, the first processing surface 1 and the second processing surface 2 are set with an accuracy of μm by the balance between the contact surface pressure and the separation force, and a minute amount between the processing surfaces 1 and 2 is set. An interval is set. The separation force includes the fluid pressure and viscosity of the fluid to be processed, the centrifugal force due to the rotation of the processing portion, the negative pressure when the urging fluid introduction portion 44 is negatively applied, and the spring 43 being pulled. The force of the spring when it is used as a spring can be mentioned. This contact surface pressure imparting mechanism may be provided not in the second processing unit 20 but in the first processing unit 10 or in both.
　前記の離反力について、具体的に説明すると、第２処理用部２０は、前記の第２処理用面２と共に、第２処理用面２の内側（即ち、第１処理用面１と第２処理用面２との間への被処理流動体の進入口側）に位置して当該第２処理用面２に隣接する離反用調整面２３を備える。この例では、離反用調整面２３は、傾斜面として実施されているが、水平面であってもよい。被処理流動体の圧力が、離反用調整面２３に作用して、第２処理用部２０を第１処理用部１０から離反させる方向への力を発生させる。従って、離反力を発生させるための受圧面は、第２処理用面２と離反用調整面２３とになる。 The separation force will be specifically described. The second processing unit 20 is arranged inside the second processing surface 2 together with the second processing surface 2 (that is, the first processing surface 1 and the second processing surface 2). A separation adjusting surface 23 is provided adjacent to the second processing surface 2 and located on the entrance side of the fluid to be processed between the processing surface 2 and the processing surface 2. In this example, the separation adjusting surface 23 is implemented as an inclined surface, but may be a horizontal surface. The pressure of the fluid to be processed acts on the separation adjusting surface 23 to generate a force in a direction in which the second processing unit 20 is separated from the first processing unit 10. Accordingly, the pressure receiving surfaces for generating the separation force are the second processing surface 2 and the separation adjusting surface 23.
　さらに、この図１の例では、第２処理用部２０に近接用調整面２４が形成されている。この近接用調整面２４は、離反用調整面２３と軸方向において反対側の面（図１においては上方の面）であり、被処理流動体の圧力が作用して、第２処理用部２０を第１処理用部１０に接近させる方向への力を発生させる。 Further, in the example of FIG. 1, the proximity adjustment surface 24 is formed on the second processing portion 20. The proximity adjustment surface 24 is a surface opposite to the separation adjustment surface 23 in the axial direction (upper surface in FIG. 1), and the pressure of the fluid to be processed acts on the second processing portion 20. A force is generated in a direction that causes the first processing unit 10 to approach the first processing unit 10.
　なお、第２処理用面２及び離反用調整面２３に作用する被処理流動体の圧力、即ち流体圧は、メカニカルシールにおけるオープニングフォースを構成する力として理解される。処理用面１，２の接近・離反の方向、即ち第２処理用部２０の出没方向（図１においては軸方向）と直交する仮想平面上に投影した近接用調整面２４の投影面積Ａ１と、当該仮想平面上に投影した第２処理用部２０の第２処理用面２及び離反用調整面２３との投影面積の合計面積Ａ２との、面積比Ａ１／Ａ２は、バランス比Ｋと呼ばれ、前記オープニングフォースの調整に重要である。このオープニングフォースについては、前記バランスライン、即ち近接用調整面２４の面積Ａ１を変更することで、被処理流動体の圧力、即ち流体圧により調整できる。 Note that the pressure of the fluid to be processed that acts on the second processing surface 2 and the separation adjusting surface 23, that is, the fluid pressure, is understood as a force constituting an opening force in the mechanical seal. The projected area A1 of the proximity adjustment surface 24 projected on a virtual plane orthogonal to the approaching / separating direction of the processing surfaces 1 and 2, that is, the protruding and protruding direction (axial direction in FIG. 1) of the second processing unit 20 The area ratio A1 / A2 of the total area A2 of the projected areas of the second processing surface 2 and the separation adjusting surface 23 of the second processing unit 20 projected onto the virtual plane is called a balance ratio K. This is important for adjusting the opening force. The opening force can be adjusted by changing the balance line, that is, the area A1 of the adjustment surface 24 for proximity, by the pressure of the fluid to be processed, that is, the fluid pressure.
　摺動面の実面圧Ｐ、即ち、接面圧力のうち流体圧によるものは次式で計算される。
　Ｐ＝Ｐ１×（Ｋ－ｋ）＋Ｐｓ The actual pressure P of the sliding surface, that is, the contact pressure due to the fluid pressure is calculated by the following equation.
P = P1 × (K−k) + Ps
　ここでＰ１は、被処理流動体の圧力即ち流体圧を示し、Ｋは前記のバランス比を示し、ｋはオープニングフォース係数を示し、Ｐｓはスプリング及び背圧力を示す。 Here, P1 represents the pressure of the fluid to be treated, that is, the fluid pressure, K represents the balance ratio, k represents the opening force coefficient, and Ps represents the spring and back pressure.
　このバランスラインの調整により摺動面の実面圧Ｐを調整することで処理用面１，２間を所望の微小隙間量にし、被処理流動体による流動体膜を形成させ、生成物などの処理された被処理物を微細とし、また、均一な反応処理を行うのである。
　なお、図示は省略するが、近接用調整面２４を離反用調整面２３よりも広い面積を持ったものとして実施することも可能である。 By adjusting the actual surface pressure P of the sliding surface by adjusting the balance line, a desired minute gap is formed between the processing surfaces 1 and 2, and a fluid film is formed by the fluid to be processed. The processed object is made fine and a uniform reaction process is performed.
Although not shown, the proximity adjustment surface 24 may be implemented with a larger area than the separation adjustment surface 23.
　被処理流動体は、前記の微小な隙間を保持する両処理用面１，２によって強制された薄膜流体となり、環状の両処理用面１、２の外側に移動しようとする。ところが、第１処理用部１０は回転しているので、混合された被処理流動体は、環状の両処理用面１，２の内側から外側へ直線的に移動するのではなく、環状の半径方向への移動ベクトルと周方向への移動ベクトルとの合成ベクトルが被処理流動体に作用して、内側から外側へ略渦巻き状に移動する。 The fluid to be processed becomes a thin film fluid forced by the two processing surfaces 1 and 2 holding the minute gaps, and tends to move to the outside of the two annular processing surfaces 1 and 2. However, since the first processing unit 10 is rotating, the mixed fluid to be processed does not move linearly from the inside to the outside of the two processing surfaces 1 and 2, but instead has an annular radius. A combined vector of the movement vector in the direction and the movement vector in the circumferential direction acts on the fluid to be processed and moves in a substantially spiral shape from the inside to the outside.
　なお、回転軸５０は、鉛直に配置されたものに限定するものではなく、水平方向に配位されたものであってもよく、傾斜して配位されたものであってよい。被処理流動体は両処理用面１，２間の微細な間隔にて処理がなされるものであり、実質的に重力の影響を排除できるからである。また、この接面圧付与機構は、前述の第２処理用部２０を変位可能に保持するフローティング機構と併用することによって、微振動や回転アライメントの緩衝機構としても機能する。 In addition, the rotating shaft 50 is not limited to a vertically arranged shaft, and may be arranged in the horizontal direction, or may be arranged in an inclined manner. This is because the fluid to be processed is processed at a fine interval between the processing surfaces 1 and 2 and the influence of gravity can be substantially eliminated. Further, this contact surface pressure applying mechanism also functions as a buffer mechanism for fine vibration and rotational alignment when used in combination with a floating mechanism that holds the second processing portion 20 in a displaceable manner.
　第１、第２処理用部１０、２０は、その少なくともいずれか一方を、冷却或いは加熱して、その温度を調整するようにしてもよく、図１では、第１、第２処理用部１０、２０に温調機構（温度調整機構）Ｊ１，Ｊ２を設けた例を図示している。また、導入される被処理流動体を冷却或いは加熱して、その温度を調整するようにしてもよい。これらの温度は、処理された被処理物の析出のために用いることもでき、また、第１、第２処理用面１、２間における被処理流動体にベナール対流若しくはマランゴニ対流を発生させるために設定してもよい。 At least one of the first and second processing parts 10 and 20 may be cooled or heated to adjust the temperature. In FIG. 1, the first and second processing parts 10 and 10 are adjusted. , 20 are provided with temperature control mechanisms (temperature control mechanisms) J1, J2. Further, the temperature of the introduced fluid to be treated may be adjusted by cooling or heating. These temperatures can also be used for the deposition of the treated material, and also to generate Benard convection or Marangoni convection in the fluid to be treated between the first and second processing surfaces 1 and 2. May be set.
　図２に示すように、第１処理用部１０の第１処理用面１には、第１処理用部１０の中心側から外側に向けて、即ち径方向について伸びる溝状の凹部１３を形成して実施してもよい。この凹部１３の平面形状は、図２（Ｂ）へ示すように、第１処理用面１上をカーブして或いは渦巻き状に伸びるものや、図示はしないが、真っ直ぐ外方向に伸びるもの、Ｌ字状などに屈曲あるいは湾曲するもの、連続したもの、断続するもの、枝分かれするものであってもよい。また、この凹部１３は、第２処理用面２に形成するものとしても実施可能であり、第１及び第２の処理用面１，２の双方に形成するものとしても実施可能である。この様な凹部１３を形成することによりマイクロポンプ効果を得ることができ、被処理流動体を第１及び第２の処理用面１，２間に吸引することができる効果がある。 As shown in FIG. 2, a groove-like recess 13 extending from the center side of the first processing portion 10 to the outside, that is, in the radial direction is formed on the first processing surface 1 of the first processing portion 10. May be implemented. As shown in FIG. 2B, the planar shape of the recess 13 is curved or spirally extending on the first processing surface 1, or is not shown, but extends straight outward, L It may be bent or curved into a letter shape or the like, continuous, intermittent, or branched. Further, the recess 13 can be implemented as one formed on the second processing surface 2, and can also be implemented as one formed on both the first and second processing surfaces 1, 2. By forming such a recess 13, a micropump effect can be obtained, and there is an effect that the fluid to be processed can be sucked between the first and second processing surfaces 1 and 2.
　この凹部１３の基端は第１処理用部１０の内周に達することが望ましい。この凹部１３の先端は、第１処理用面１の外周面側に向けて伸びるもので、その深さ（横断面積）は、基端から先端に向かうにつれて、漸次減少するものとしている。
　この凹部１３の先端と第１処理用面１の外周面との間には、凹部１３のない平坦面１６が設けられている。 It is desirable that the base end of the recess 13 reaches the inner periphery of the first processing unit 10. The tip of the recess 13 extends toward the outer peripheral surface of the first processing surface 1, and the depth (cross-sectional area) gradually decreases from the base end toward the tip.
A flat surface 16 without the recess 13 is provided between the tip of the recess 13 and the outer peripheral surface of the first processing surface 1.
　前述の第２導入部ｄ２の開口部ｄ２０を第２処理用面２に設ける場合は、対向する前記第１処理用面１の平坦面１６と対向する位置に設けることが好ましい。 When the opening d20 of the second introduction part d2 is provided in the second processing surface 2, it is preferably provided at a position facing the flat surface 16 of the opposing first processing surface 1.
　この開口部ｄ２０は、第１処理用面１の凹部１３からよりも下流側（この例では外側）に設けることが望ましい。特に、マイクロポンプ効果によって導入される際の流れ方向が処理用面間で形成されるスパイラル状で層流の流れ方向に変換される点よりも外径側の平坦面１６に対向する位置に設置することが望ましい。具体的には、図２（Ｂ）において、第１処理用面１に設けられた凹部１３の最も外側の位置から、径方向への距離ｎを、約０．５ｍｍ以上とするのが好ましい。特に、流体中から微粒子を析出させる場合には、層流条件下にて複数の被処理流動体の混合と、微粒子の析出が行なわれることが望ましい。 The opening d20 is desirably provided on the downstream side (outside in this example) from the concave portion 13 of the first processing surface 1. In particular, it is installed at a position facing the flat surface 16 on the outer diameter side from the point where the flow direction when introduced by the micropump effect is converted into a laminar flow direction in a spiral shape formed between the processing surfaces. It is desirable to do. Specifically, in FIG. 2B, the distance n in the radial direction from the outermost position of the recess 13 provided in the first processing surface 1 is preferably about 0.5 mm or more. In particular, when depositing fine particles from a fluid, it is desirable to mix a plurality of fluids to be treated and deposit fine particles under laminar flow conditions.
　開口部ｄ２０の形状は、図２（Ｂ）や図３（Ｂ）に示すように円形状であってもよく、図示しないが、リング状ディスクである処理用面２の中央の開口を取り巻く同心円状の円環形状であってもよい。また、開口部を円環形状とした場合、その円環形状の開口部は連続していてもよいし、不連続であってもよい。
　円環形状の開口部ｄ２０を処理用面２の中央の開口を取り巻く同心円状に設けると、第２流体を処理用面１，２間に導入する際に円周方向において同一条件で実施することができるため、微粒子を量産したい場合には、開口部の形状を同心円状の円環形状とすることが好ましい。 The shape of the opening d20 may be circular as shown in FIGS. 2B and 3B, and although not shown, a concentric circle surrounding the central opening of the processing surface 2 that is a ring-shaped disk. An annular shape may be used. Further, when the opening has an annular shape, the annular opening may be continuous or discontinuous.
When the annular opening d20 is provided concentrically around the central opening of the processing surface 2, the second fluid is introduced under the same conditions in the circumferential direction when introduced between the processing surfaces 1 and 2. Therefore, when mass production of fine particles is desired, it is preferable that the shape of the opening is a concentric ring shape.
　この第２導入部ｄ２は方向性を持たせることができる。例えば、図３（Ａ）に示すように、前記の第２処理用面２の開口部ｄ２０からの導入方向が、第２処理用面２に対して所定の仰角（θ１）で傾斜している。この仰角（θ１）は、０度を超えて９０度未満に設定されており、さらに反応速度が速い反応の場合には１度以上４５度以下で設置されるのが好ましい。 The second introduction part d2 can have directionality. For example, as shown in FIG. 3A, the introduction direction from the opening d20 of the second processing surface 2 is inclined with respect to the second processing surface 2 at a predetermined elevation angle (θ1). . The elevation angle (θ1) is set to be more than 0 degrees and less than 90 degrees, and in the case of a reaction with a higher reaction rate, it is preferably set at 1 to 45 degrees.
　また、図３（Ｂ）に示すように、前記の第２処理用面２の開口部ｄ２０からの導入方向が、前記の第２処理用面２に沿う平面において、方向性を有するものである。この第２流体の導入方向は、処理用面の半径方向の成分にあっては中心から遠ざかる外方向であって、且つ、回転する処理用面間における流体の回転方向に対しての成分にあっては順方向である。言い換えると、開口部ｄ２０を通る半径方向であって外方向の線分を基準線ｇとして、この基準線ｇから回転方向Ｒへの所定の角度（θ２）を有するものである。この角度（θ２）についても、０度を超えて９０度未満に設定されることが好ましい。 Further, as shown in FIG. 3B, the introduction direction from the opening d20 of the second processing surface 2 has directionality in the plane along the second processing surface 2. . The introduction direction of the second fluid is a component in the radial direction of the processing surface that is an outward direction away from the center and a component with respect to the rotation direction of the fluid between the rotating processing surfaces. Is forward. In other words, a line segment in the radial direction passing through the opening d20 and extending outward is defined as a reference line g and has a predetermined angle (θ2) from the reference line g to the rotation direction R. This angle (θ2) is also preferably set to more than 0 degree and less than 90 degrees.
　この角度（θ２）は、流体の種類、反応速度、粘度、処理用面の回転速度などの種々の条件に応じて、変更して実施することができる。また、第２導入部ｄ２に方向性を全く持たせないこともできる。 This angle (θ2) can be changed and implemented in accordance with various conditions such as the type of fluid, reaction speed, viscosity, and rotational speed of the processing surface. In addition, the second introduction part d2 may not have any directionality.
　前記の被処理流動体の種類とその流路の数は、図１の例では、２つとしたが、１つであってもよく、３つ以上であってもよい。図１の例では、第２導入部ｄ２から処理用面１，２間に第２流体を導入したが、この導入部は、第１処理用部１０に設けてもよく、双方に設けてもよい。また、一種類の被処理流動体に対して、複数の導入部を用意してもよい。また、各処理用部に設けられる導入用の開口部は、その形状や大きさや数は特に制限はなく適宜変更して実施し得る。また、前記第１及び第２の処理用面間１、２の直前或いはさらに上流側に導入用の開口部を設けてもよい。 In the example of FIG. 1, the number of fluids to be treated and the number of flow paths are two, but may be one, or may be three or more. In the example of FIG. 1, the second fluid is introduced between the processing surfaces 1 and 2 from the second introduction part d2, but this introduction part may be provided in the first processing part 10 or provided in both. Good. Moreover, you may prepare several introduction parts with respect to one type of to-be-processed fluid. In addition, the shape, size, and number of the opening for introduction provided in each processing portion are not particularly limited, and can be appropriately changed. An opening for introduction may be provided immediately before or between the first and second processing surfaces 1 and 2 or further upstream.
　なお、処理用面１，２間にて前記処理を行う事が出来れば良いので、前記とは逆に、第１導入部ｄ１より第２流体を導入し、第２導入部ｄ２より第１流体を導入するものであっても良い。つまり、各流体における第１、第２という表現は、複数存在する流体の第ｎ番目であるという、識別のための意味合いを持つに過ぎないものであり、第３以上の流体も存在し得る。 In addition, since it is sufficient if the processing can be performed between the processing surfaces 1 and 2, the second fluid is introduced from the first introduction part d1 and the first fluid is introduced from the second introduction part d2, contrary to the above. May be introduced. In other words, the expressions “first” and “second” in each fluid have only an implication for identification that they are the nth of a plurality of fluids, and a third or higher fluid may exist.
　前記装置においては、析出・沈殿または結晶化のような処理が、図１に示すように、接近・離反可能に互いに対向して配設され、少なくとも一方が他方に対して回転する処理用面１、２の間で強制的に均一混合しながら起こる。処理された被処理物の粒子径や単分散度は処理用部１０、２０の回転数や流速、処理用面１，２間の距離や、被処理流動体の原料濃度、または被処理流動体の溶媒種等を適宜調整することにより、制御することができる。 In the apparatus, as shown in FIG. 1, processes such as precipitation / precipitation or crystallization are disposed so as to be able to approach and separate from each other, and at least one of the processing surfaces 1 rotates with respect to the other. Occurs with forcible uniform mixing between the two. The particle size and monodispersity of the processed material to be processed are the rotational speed and flow velocity of the processing parts 10 and 20, the distance between the processing surfaces 1 and 2, the raw material concentration of the processed fluid, or the processed fluid. It can be controlled by appropriately adjusting the solvent species and the like.
　以下、前記の装置を用いて行う微粒子の製造方法の具体的な態様について説明する。 Hereinafter, specific embodiments of the method for producing fine particles performed using the above-described apparatus will be described.
　前記の装置において、少なくとも１種類の微粒子原料を溶媒に溶解させた微粒子原料溶液と、少なくとも１種類の析出溶媒とを、対向して配設された、接近・離反可能な、少なくとも一方が他方に対して相対的に回転する少なくとも２つの処理用面間に導入し、少なくとも２つの処理用面間に形成される薄膜流体中で混合して、微粒子を析出させる。その際、回転する攪拌翼を有する攪拌機を用いて微粒子原料溶液の調製を行い、攪拌エネルギーを規定する３つの条件（攪拌時間、攪拌翼の周速度、微粒子原料溶液の温度）のうち少なくとも１つを変化させることにより、攪拌エネルギーを増減させるものとする。 In the above apparatus, at least one kind of fine particle raw material solution in which at least one kind of fine particle raw material is dissolved in a solvent and at least one kind of precipitation solvent are arranged to face each other, and at least one of them is the other. It introduce | transduces between the at least 2 process surfaces which rotate relatively, and mixes in the thin film fluid formed between at least 2 process surfaces, and deposits microparticles | fine-particles. At this time, the fine particle raw material solution is prepared using a stirrer having a rotating stirring blade, and at least one of three conditions (stirring time, peripheral speed of the stirring blade, and temperature of the fine particle raw material solution) for defining the stirring energy. The stirring energy is increased or decreased by changing.
　前記の微粒子の析出反応は、本願の図１に示す装置の、接近・離反可能に互いに対向して配設され、少なくとも一方が他方に対して回転する処理用面１，２間で強制的に均一混合しながら起こる。 The fine particle precipitation reaction of the apparatus shown in FIG. 1 of the present application is forcibly arranged between the processing surfaces 1 and 2 which are arranged so as to be able to approach and separate from each other and at least one rotates with respect to the other. Occurs with uniform mixing.
　まず、一つの流路である第１導入部ｄ１より、第１流体として少なくとも１種類の析出溶媒を、接近・離反可能に互いに対向して配設され、少なくとも一方が他方に対して回転する処理用面１，２間に導入して、この処理用面間に第１流体から構成された薄膜流体である第１流体膜を作る。 First, a process in which at least one kind of precipitation solvent as a first fluid is disposed to face each other so as to be able to approach and separate from the first introduction part d1 which is one flow path, and at least one rotates with respect to the other. It introduce | transduces between the use surfaces 1 and 2, and makes the 1st fluid film | membrane which is a thin film fluid comprised from the 1st fluid between this process surface.
　次いで別流路である第２導入部ｄ２より、第２流体として少なくとも１種類の微粒子原料を溶媒に溶解した微粒子原料溶液を、前記処理用面１，２間に作られた第１流体膜に直接導入する。 Next, a fine particle material solution obtained by dissolving at least one kind of fine particle material in a solvent as a second fluid is applied to the first fluid film formed between the processing surfaces 1 and 2 from the second introduction part d2 which is a separate channel. Install directly.
　前記のように、被処理流動体の供給圧と回転する処理用面の間にかかる圧力との圧力バランスによって距離を固定された処理用面１，２間にて、第１流体と第２流体とが混合され、微粒子の析出反応を行う事が出来る。 As described above, the first fluid and the second fluid are disposed between the processing surfaces 1 and 2 whose distance is fixed by the pressure balance between the supply pressure of the fluid to be processed and the pressure applied between the rotating processing surfaces. Can be mixed to perform precipitation reaction of fine particles.
　なお、処理用面１，２間にて前記反応を行う事が出来れば良いので、前記とは逆に、第１導入部ｄ１より第２流体を導入し、第２導入部ｄ２より第１流体を導入するものであっても良い。つまり、各流体における第１、第２という表現は、複数存在する流体の第ｎ番目であるという、識別のための意味合いを持つに過ぎないものであり、第３以上の流体も存在し得る。 In addition, since it is sufficient that the reaction can be performed between the processing surfaces 1 and 2, the second fluid is introduced from the first introduction part d1 and the first fluid is introduced from the second introduction part d2, contrary to the above. May be introduced. In other words, the expressions “first” and “second” in each fluid have only an implication for identification that they are the nth of a plurality of fluids, and a third or higher fluid may exist.
　前述のように、第１導入部ｄ１、第２導入部ｄ２以外に第３導入部ｄ３を処理装置に設けることもでき、この場合にあっては、例えば各導入部から、第１流体、第２流体、第１流体及び第２流体とは異なる第３の流体をそれぞれ別々に処理装置に導入することが可能である。そうすると、各溶液の濃度や圧力を個々に管理することができ、析出反応をより精密に制御することができる。なお、各導入部へ導入する被処理流動体（第１流体～第３流体）の組み合わせは、任意に設定できる。第４以上の導入部を設けた場合も同様であって、このように処理装置へ導入する流体を細分化できる。
　さらに、第１、第２流体等の被処理流動体の温度を制御したり、第１流体と第２流体等との温度差（即ち、供給する各被処理流動体の温度差）を制御することもできる。供給する各被処理流動体の温度や温度差を制御するために、各被処理流動体の温度（処理装置、より詳しくは、処理用面１，２間に導入される直前の温度）を測定し、処理用面１，２間に導入される各被処理流動体の加熱又は冷却を行う機構を付加して実施することも可能である。 As described above, in addition to the first introduction part d1 and the second introduction part d2, the third introduction part d3 can be provided in the processing apparatus. In this case, for example, the first fluid, the first fluid is supplied from each introduction part. A third fluid different from the two fluids, the first fluid, and the second fluid can be separately introduced into the processing apparatus. If it does so, the density | concentration and pressure of each solution can be managed separately, and precipitation reaction can be controlled more precisely. Note that the combination of fluids to be processed (first fluid to third fluid) to be introduced into each introduction portion can be arbitrarily set. The same applies to the case where the fourth or more introduction portions are provided, and the fluid to be introduced into the processing apparatus can be subdivided in this way.
Further, the temperature of the fluid to be processed such as the first and second fluids is controlled, and the temperature difference between the first fluid and the second fluid (that is, the temperature difference between the supplied fluids to be processed) is controlled. You can also In order to control the temperature and temperature difference of each processed fluid to be supplied, the temperature of each processed fluid (processing device, more specifically, the temperature immediately before being introduced between the processing surfaces 1 and 2) is measured. It is also possible to add a mechanism for heating or cooling each fluid to be processed introduced between the processing surfaces 1 and 2.
　次に述べる顔料微粒子の析出反応が、接近・離反可能に互いに対向して配設され、少なくとも一方が他方に対して回転する処理用面１，２の間で強制的に均一混合しながら起こる。顔料微粒子の粒子径や単分散度の制御、並びに結晶型の種類は処理用部１０，２０の回転数や流速及び処理用面間の距離や、原料濃度等を変えることにより、調節することができる。この点は、特許４６９１６９８等において、本願出願人が指摘している通りであり、本願出願人は、析出ステップに重点をおいて、回転数、流速、処理用面間の距離を調整することによって、目的の物性や性能を有する微粒子の製造に取り組んできた。ところが、溶解ステップの調整、特に、攪拌エネルギーの増減によって、析出ステップに送られる流体の溶解の状態を調整することにて、析出ステップで得られる微粒子の結晶化度や結晶型を制御し得ることを知見して、本発明を完成したものである。これによって、析出ステップの条件を固定したまま、溶解ステップの条件を変更するだけで、微粒子の結晶化度や結晶型を変化させ、目的の微粒子の性状や性能を得ることができたり、溶解ステップと析出ステップとの両方の条件を変化させることで、目的の微粒子の性状や性能を、よりダイナミックに変更することができるようになったものである。 The pigment fine particle precipitation reaction described below occurs while being forcibly and uniformly mixed between the processing surfaces 1 and 2 which are disposed so as to be able to approach and separate from each other and at least one rotates relative to the other. Control of the particle size and monodispersity of the pigment fine particles, and the type of crystal type can be adjusted by changing the rotational speed, flow rate, distance between processing surfaces, raw material concentration, etc. of the processing units 10 and 20. it can. This point is as pointed out by the present applicant in Patent 4916698 and the like, and the present applicant emphasizes the precipitation step and adjusts the rotation speed, flow rate, and distance between the processing surfaces. We have been working on the production of fine particles with the desired physical properties and performance. However, it is possible to control the crystallinity and crystal form of the fine particles obtained in the precipitation step by adjusting the dissolution step, particularly by adjusting the dissolution state of the fluid sent to the precipitation step by increasing or decreasing the stirring energy. Thus, the present invention has been completed. This makes it possible to change the crystallinity and crystal form of the fine particles by changing the conditions of the dissolution step while fixing the conditions of the precipitation step, and to obtain the properties and performance of the desired fine particles. By changing the conditions of both the precipitation step and the precipitation step, the properties and performance of the target fine particles can be changed more dynamically.
　顔料微粒子の析出反応については、顔料原末を硫酸、硝酸、塩酸などの強酸に溶解し、調整された顔料酸性溶液を、水又は有機溶媒を含む溶液と混合して顔料微粒子を得るアシッドペースティング法や顔料原末をアルカリ溶液に溶解し、調整された顔料アルカリ溶液を、水又は有機溶媒を含む溶液と混合して顔料微粒子を得るアルカリペースト法、再沈法、ｐＨ調整法、貧溶媒法等の種々の液相法を用いることができる。
　これらの析出反応は、例えば、特許文献３に記載されるような、従来周知の方法で実施することができる。
　以下に、前記装置を用いて顔料微粒子が生成する反応をより詳細に説明する。 For the pigment fine particle precipitation reaction, acid pasting is obtained by dissolving the pigment bulk powder in a strong acid such as sulfuric acid, nitric acid, hydrochloric acid, etc., and mixing the prepared pigment acidic solution with a solution containing water or an organic solvent. Alkali paste method, reprecipitation method, pH adjustment method, anti-solvent method to obtain pigment fine particles by dissolving the method and pigment powder in an alkali solution and mixing the prepared pigment alkali solution with a solution containing water or an organic solvent Various liquid phase methods such as can be used.
These precipitation reactions can be carried out by a conventionally known method as described in Patent Document 3, for example.
Hereinafter, the reaction of producing pigment fine particles using the above apparatus will be described in more detail.
（アシッドペースティング法）
　前記装置をアシッドペースティング法に用いる場合にはまず、一つの流路である第１導入部ｄ１より、第１流体として水又は有機溶媒を含む溶液を、接近・離反可能に互いに対向して配設され、少なくとも一方が他方に対して回転する処理用面１，２間に導入して、この処理用面間に第１流体から構成された薄膜流体を形成する。 (Acid pasting method)
When the apparatus is used in the acid pasting method, first, a solution containing water or an organic solvent as a first fluid is disposed opposite to each other so as to be able to approach and separate from the first introduction part d1 which is one flow path. A thin film fluid composed of a first fluid is formed between the processing surfaces 1 and 2 between the processing surfaces 1 and 2 that are provided and at least one rotates with respect to the other.
　次いで別流路である第２導入部ｄ２より、第２流体として、反応物である顔料物質を溶解した酸を含む流体（顔料酸性溶液）を、前記第１流体から構成された薄膜流体に直接導入する。 Next, from the second introduction part d2 which is a separate flow path, a fluid (pigment acid solution) containing an acid in which a pigment substance as a reactant is dissolved as a second fluid is directly applied to the thin film fluid composed of the first fluid. Introduce.
　前記のように、流体の供給圧と回転する処理用面の間にかかる圧力との圧力バランスによって距離を固定された処理用面１，２間にて、第１流体と第２流体とが超薄膜状態を維持したまま、瞬間的に混合され、顔料微粒子が生成する反応を行う事が出来る。 As described above, the first fluid and the second fluid exceed each other between the processing surfaces 1 and 2 whose distance is fixed by the pressure balance between the fluid supply pressure and the pressure applied between the rotating processing surfaces. While maintaining the thin film state, it is possible to carry out a reaction that is instantaneously mixed to produce pigment fine particles.
　なお、処理用面１，２間にて前記反応を行う事が出来れば良いので、前記とは逆に、第１導入部ｄ１より第２流体を導入し、第２導入部ｄ２より第１流体を導入するものであっても良い。つまり、各溶媒における第１、第２という表現は、複数存在する溶媒の第ｎ番目であるという、識別のための意味合いを持つに過ぎないものであり、第３以上の溶媒も存在し得る。 In addition, since it is sufficient that the reaction can be performed between the processing surfaces 1 and 2, the second fluid is introduced from the first introduction part d1 and the first fluid is introduced from the second introduction part d2, contrary to the above. May be introduced. In other words, the expressions “first” and “second” in each solvent only have a meaning for identification that they are the n-th of a plurality of solvents, and third or more solvents may exist.
　第１流体は前述どおり、水、又は有機溶媒を含む溶液である。水としてはイオン交換水、純水、または蒸留水などの精製した水が好ましい。また、水、又は有機溶媒を含む溶液をアルカリ性にしたアルカリ溶液を用いてもよく、前記水、又は有機溶媒を含む溶液をアルカリ性とする場合、アンモニア水、水酸化ナトリウム水溶液、水酸化カリウム水溶液などを例として用いることができる。メタノールやエタノール、プロパノールを用いてもよい。 As described above, the first fluid is water or a solution containing an organic solvent. The water is preferably purified water such as ion exchange water, pure water, or distilled water. Moreover, you may use the alkaline solution which made the solution containing water or an organic solvent alkaline, and when making the solution containing the said water or an organic solvent alkaline, ammonia water, sodium hydroxide aqueous solution, potassium hydroxide aqueous solution, etc. Can be used as an example. Methanol, ethanol, or propanol may be used.
　第２流体に用いられる酸としては、顔料に対する溶解性を示せば問題なく、特に限定されないが、例えば酸性水溶液の場合は硫酸、塩酸、硝酸、トリフルオロ酢酸を用いる事ができる。好ましくは強酸、特に95%以上の濃硫酸を用いる事ができる。 The acid used in the second fluid is not particularly limited as long as it shows solubility in the pigment and is not particularly limited. For example, in the case of an acidic aqueous solution, sulfuric acid, hydrochloric acid, nitric acid, and trifluoroacetic acid can be used. Preferably, a strong acid, particularly 95% or more of concentrated sulfuric acid can be used.
　さらに、第１流体もしくは第２流体に、顔料の結晶型の制御や顔料の品質コントロールなどの目的のために有機溶剤を混合してもよい。有機溶剤としては公知のものが使用できる。また、有機溶剤以外にも、ブロック共重合体や高分子ポリマー、界面活性剤などの分散剤を含んでもよい。 Furthermore, an organic solvent may be mixed with the first fluid or the second fluid for the purpose of controlling the crystal type of the pigment or controlling the quality of the pigment. Known organic solvents can be used. Further, in addition to the organic solvent, a dispersant such as a block copolymer, a polymer, or a surfactant may be included.
（再沈法）
　次に、前記装置を再沈法に用いる場合にはまず、一つの流路である第１導入部ｄ１より、第１流体として顔料に対して貧溶媒となり、後記溶媒とは相溶性である溶媒を、接近・離反可能に互いに対向して配設され、少なくとも一方が他方に対して回転する処理用面１，２間に導入して、この処理用面１，２間に第１流体から構成された薄膜流体を形成する。 (Reprecipitation method)
Next, when the apparatus is used for the reprecipitation method, first, from the first introduction part d1 which is one flow path, the solvent becomes a poor solvent for the pigment as the first fluid and is compatible with the solvent described later. Are disposed between the processing surfaces 1 and 2 which are arranged so as to be able to approach and separate from each other and at least one of which is rotated with respect to the other. Forming a thin film fluid.
　次いで別流路である第２導入部ｄ２より、第２流体として顔料物質を溶解した有機溶媒を含む流体を、前記第１流体から構成された薄膜流体に直接導入する。 Next, a fluid containing an organic solvent in which a pigment substance is dissolved as a second fluid is directly introduced into the thin film fluid composed of the first fluid from the second introduction part d2 which is a separate flow path.
　前記のように、流体の供給圧と処理用面１，２の間にかかる圧力との圧力バランスによって距離を固定された処理用面１，２間にて第１流体と第２流体が超薄膜状態を維持したまま、瞬間的に混合され、顔料微粒子が生成する反応を行う事が出来る。 As described above, the first fluid and the second fluid are ultrathin between the processing surfaces 1 and 2 that are fixed in distance by the pressure balance between the fluid supply pressure and the pressure applied between the processing surfaces 1 and 2. While maintaining the state, it is possible to carry out a reaction that is instantaneously mixed to produce pigment fine particles.
　なお、処理用面１，２間にて前記反応を行う事が出来れば良いので、前記とは逆に、第１導入部ｄ１より第２流体を導入し、第２導入部ｄ２より第１流体を導入するものであっても良い。つまり、各溶媒における第１、第２という表現は、複数存在する溶媒の第ｎ番目であるという、識別のための意味合いを持つに過ぎないものであり、第３以上の溶媒も存在し得る。 In addition, since it is sufficient that the reaction can be performed between the processing surfaces 1 and 2, the second fluid is introduced from the first introduction part d1 and the first fluid is introduced from the second introduction part d2, contrary to the above. May be introduced. In other words, the expressions “first” and “second” in each solvent only have a meaning for identification that they are the n-th of a plurality of solvents, and third or more solvents may exist.
　第１流体としては前述どおり、顔料に対して貧溶媒で第２流体を形成する顔料を溶解する溶媒とは相溶性であれば特に限定されないが、水、アルコール系溶媒、ケトン系溶媒、エーテル系溶媒、芳香族系溶媒、二硫化炭素、脂肪族系溶媒、ニトリル系溶媒、スルホキシド系溶媒、ハロゲン系溶媒、エステル系溶媒、イオン性液体、またはこれら２種以上の混合溶媒から選択されることが好ましい。 As described above, the first fluid is not particularly limited as long as it is compatible with the solvent that dissolves the pigment that forms the second fluid with a poor solvent for the pigment, but water, alcohol solvents, ketone solvents, ether solvents Solvent, aromatic solvent, carbon disulfide, aliphatic solvent, nitrile solvent, sulfoxide solvent, halogen solvent, ester solvent, ionic liquid, or a mixture of two or more of these preferable.
　第２流体に用いられる有機溶媒としては顔料に対する溶解性を示せば問題なく、特に限定されないが、好ましくは１－メチル－２－ピロリジノン、１，３－ジメチル－２－イミダゾリジノン、２－ピロリジノン、ε－カプロラクタム、ホルムアミド、Ｎ－メチルホルムアミド、Ｎ，Ｎ－ジメチルホルムアミド、アセトアミド、Ｎ－メチルアセトアミド、Ｎ，Ｎ－ジメチルアセトアミド、Ｎ－メチルプロパンアミド、ヘキサメチルホスホリックトリアミドのようなアミド系溶媒を用いる事ができる。 The organic solvent used in the second fluid is not particularly limited as long as it shows solubility in pigments, but is preferably 1-methyl-2-pyrrolidinone, 1,3-dimethyl-2-imidazolidinone, 2-pyrrolidinone. Amide systems such as ε-caprolactam, formamide, N-methylformamide, N, N-dimethylformamide, acetamide, N-methylacetamide, N, N-dimethylacetamide, N-methylpropanamide, hexamethylphosphoric triamide A solvent can be used.
　さらに、第１流体もしくは第２流体に、ブロック共重合体や高分子ポリマー、界面活性剤などの分散剤を含んでもよい。 Furthermore, the first fluid or the second fluid may contain a dispersing agent such as a block copolymer, a polymer, or a surfactant.
（pＨ調整法）
　次に、前記装置をpＨ調整法に用いる場合にはまず、一つの流路である第１導入部ｄ１より、第１流体として、pＨを変化させる顔料析出用溶液を、前記の回転する処理用面１，２間に導入して、この処理用面間に第１流体から構成された薄膜流体を形成する。 (PH adjustment method)
Next, when the apparatus is used for the pH adjustment method, first, a pigment precipitation solution that changes pH is used as the first fluid from the first introduction part d1 that is one flow path for the rotating process. Introduced between the surfaces 1 and 2, a thin film fluid composed of the first fluid is formed between the processing surfaces.
　次いで別流路である第２導入部ｄ２より、第２流体として、酸性またはアルカリ性であるpＨ調整溶液或いは前記pＨ調整溶液と有機溶媒との混合溶液のいずれかに、少なくとも１種類の顔料を溶解した顔料溶液を、前記第１流体から構成された薄膜流体に直接導入する。 Subsequently, at least one kind of pigment is dissolved in the acidic fluid or alkaline pH adjusting solution or the mixed solution of the pH adjusting solution and the organic solvent as the second fluid from the second introduction part d2 which is another flow path. The pigment solution thus prepared is directly introduced into the thin film fluid composed of the first fluid.
　前記のように、流体の供給圧と回転する処理用面１，２の間にかかる圧力との圧力バランスによって距離を制御された処理用面１，２間にて、第１流体と第２流体とが薄膜状態を維持したまま、瞬間的に混合され、顔料微粒子が生成する反応を行う事が出来る。 As described above, the first fluid and the second fluid are disposed between the processing surfaces 1 and 2 whose distance is controlled by the pressure balance between the fluid supply pressure and the pressure applied between the rotating processing surfaces 1 and 2. Can be mixed instantaneously while maintaining the thin film state, and a reaction to form pigment fine particles can be performed.
　具体的には、例えば、ある有機溶媒にほとんど溶解しない有機顔料を、前記の有機溶媒にアルカリの物質を加えたアルカリ性の溶液に加えることで溶解させて有機顔料溶液（第２流体）とし、その有機顔料溶液を水、若しくは他の有機溶媒、若しくは前記アルカリの物質を含まない有機溶媒、若しくは酸を含む溶媒が用いられた顔料析出用溶液（第１流体）に加える事で、有機顔料溶液のｐＨが変化し、顔料が析出する反応を処理用面１，２間にて行う事が出来る。この場合、加えられる酸とアルカリは、顔料種に応じて、顔料を溶解するために加えるか、析出させるために加えるかを選択すればよい。 Specifically, for example, an organic pigment that hardly dissolves in a certain organic solvent is dissolved in an alkaline solution obtained by adding an alkaline substance to the organic solvent to obtain an organic pigment solution (second fluid). By adding the organic pigment solution to water, another organic solvent, an organic solvent not containing the alkaline substance, or a pigment precipitation solution (first fluid) using an acid-containing solvent, the organic pigment solution The reaction in which the pH changes and the pigment precipitates can be performed between the processing surfaces 1 and 2. In this case, the acid and alkali to be added may be selected to be added to dissolve or precipitate the pigment depending on the pigment type.
　なお、処理用面１，２間にて前記反応を行う事が出来れば良いので、前記とは逆に、第１導入部ｄ１より第２流体を導入し、第２導入部ｄ２より第１流体を導入するものであっても良い。つまり、各流体における第１、第２という表現は、複数存在する流体の第ｎ番目であるという、識別のための意味合いを持つに過ぎないものであり、第３以上の流体も存在し得る。 In addition, since it is sufficient that the reaction can be performed between the processing surfaces 1 and 2, the second fluid is introduced from the first introduction part d1 and the first fluid is introduced from the second introduction part d2, contrary to the above. May be introduced. In other words, the expressions “first” and “second” in each fluid have only an implication for identification that they are the nth of a plurality of fluids, and a third or higher fluid may exist.
　第１流体とされた顔料析出用溶液は前述どおり、前記顔料溶液のｐＨを変化させることのできる溶液であり、析出を目的とする顔料に溶解性を示さない、若しくは、第２流体とされた顔料溶液に含まれる溶媒よりも顔料に対する溶解性が小さいものであれば特に限定されないが、水もしくは有機溶媒、若しくはそれらの混合物からなる。水としてはイオン交換水、純水、または蒸留水などの精製された水が好ましい。有機溶媒としては、特に限定されないが、メタノール、エタノール、イソプロパノール、ｔ－ブタノールに代表される一価のアルコール系溶媒、エチレングリコール、プロピレングリコール、ジエチレングリコール、ポリエチレングリコール、チオジグリコール、ジチオジグリコール、2－メチル－1，3－プロパンジオール、1，2，6－ヘキサントリオール、アセチレングリコール誘導体、グリセリン、もしくはトリメチロールプロパン等に代表される多価アルコール系溶媒、１－メチル－２－ピロリジノン、１，３－ジメチル－２－イミダゾリジノン、２－ピロリジノン、ε－カプロラクタム、ホルムアミド、Ｎ－メチルホルムアミド、Ｎ，Ｎ－ジメチルホルムアミド、アセトアミド、Ｎ－メチルアセトアミド、Ｎ，Ｎ－ジメチルアセトアミド、Ｎ－メチルプロパンアミド、ヘキサメチルホスホリックトリアミド、尿素、もしくはテトラメチル尿素等のようなアミド系溶媒、その他、エチレングリコールモノメチル（又はエチル）エーテル、ジエチレングリコールモノメチル（又はエチル）エーテル、もしくはトリエチレングリコールモノエチル（又はブチル）エーテル等の多価アルコールの低級モノアルキルエーテル系溶媒、エチレングリコールジメチルエーテル（モノグライム）、ジエチレングリコールジメチルエーテル（ジグライム）、もしくはトリエチレングリコールジメチルエーテル（トリグライム）等のポリエーテル系溶媒、スルホラン、ジメチルスルホキシド、もしくは3－スルホレン等の含イオウ系溶媒、ジアセトンアルコール、ジエタノールアミン等の多官能系溶媒、酢酸、マレイン酸、ドコサヘキサエン酸、トリクロロ酢酸、もしくはトリフルオロ酢酸等のカルボン酸系溶媒、メタンスルホン酸、もしくはトリフルオロスルホン酸等のスルホン酸系溶媒、ベンゼン、トルエン、キシレン等のベンゼン系溶媒等が挙げられる。 As described above, the pigment deposition solution that is the first fluid is a solution that can change the pH of the pigment solution, and does not exhibit solubility in the pigment intended for deposition, or is a second fluid. Although it will not specifically limit if the solubility with respect to a pigment is smaller than the solvent contained in a pigment solution, It consists of water, an organic solvent, or mixtures thereof. The water is preferably purified water such as ion exchange water, pure water, or distilled water. The organic solvent is not particularly limited, but is a monohydric alcohol solvent represented by methanol, ethanol, isopropanol, t-butanol, ethylene glycol, propylene glycol, diethylene glycol, polyethylene glycol, thiodiglycol, dithiodiglycol, 2 Polyhydric alcohol solvents such as methyl-1,3-propanediol, 1,2,6-hexanetriol, acetylene glycol derivatives, glycerin or trimethylolpropane, 1-methyl-2-pyrrolidinone, 1, 3-dimethyl-2-imidazolidinone, 2-pyrrolidinone, ε-caprolactam, formamide, N-methylformamide, N, N-dimethylformamide, acetamide, N-methylacetamide, N, N-dimethylacetamide Amide solvents such as N-methylpropanamide, hexamethylphosphoric triamide, urea, tetramethylurea, etc., ethylene glycol monomethyl (or ethyl) ether, diethylene glycol monomethyl (or ethyl) ether, or triethylene glycol Lower monoalkyl ether solvents of polyhydric alcohols such as monoethyl (or butyl) ether, polyether solvents such as ethylene glycol dimethyl ether (monoglyme), diethylene glycol dimethyl ether (diglyme), or triethylene glycol dimethyl ether (triglyme), sulfolane, Sulfur-containing solvents such as dimethyl sulfoxide or 3-sulfolene, polyfunctional solvents such as diacetone alcohol and diethanolamine Carboxylic acid solvents such as acetic acid, maleic acid, docosahexaenoic acid, trichloroacetic acid, or trifluoroacetic acid, sulfonic acid solvents such as methanesulfonic acid or trifluorosulfonic acid, benzene solvents such as benzene, toluene, xylene, etc. Can be mentioned.
　さらに、溶媒に酸又はアルカリであるpＨ調整物質を加えた、酸性またはアルカリ性であるpＨ調整溶液としても実施できる。その場合のpＨ調整物質は特に限定されないが、アルカリの場合は、水酸化リチウム、水酸化ナトリウム、水酸化カリウム、水酸化カルシウム、もしくは水酸化バリウムなどの無機塩基、またはトリアルキルアミン、ジアザビシクロウンデセン、金属アルコキシドなどの有機アルカリである。酸の場合には、ギ酸、硝酸、硫酸、塩酸、もしくは燐酸などの無機酸、または酢酸、トリフルオロ酢酸、シュウ酸、メタンスルホン酸、もしくはトリフルオロメタンスルホン酸などの有機酸である。それらを固体状態で加えても良いし、水溶液や有機溶媒溶液として加えても実施できる。 Furthermore, it can also be carried out as an acidic or alkaline pH adjusting solution obtained by adding an acid or alkaline pH adjusting substance to a solvent. In this case, the pH adjusting substance is not particularly limited. In the case of an alkali, an inorganic base such as lithium hydroxide, sodium hydroxide, potassium hydroxide, calcium hydroxide, or barium hydroxide, or a trialkylamine, diazabicyclo is used. Organic alkali such as undecene and metal alkoxide. In the case of an acid, it is an inorganic acid such as formic acid, nitric acid, sulfuric acid, hydrochloric acid, or phosphoric acid, or an organic acid such as acetic acid, trifluoroacetic acid, oxalic acid, methanesulfonic acid, or trifluoromethanesulfonic acid. They may be added in a solid state, or may be carried out by adding them as an aqueous solution or an organic solvent solution.
　第２流体とされた顔料溶液に用いられる溶媒としても、第１流体と同様の溶媒を用いることができる。ただし、第１流体に含まれる溶媒よりも顔料に対する溶解性が大きいものを選択するのが好ましい。そして、pＨ調整物質としても第１流体と同様の物質を加えて実施できる。第２流体が第１流体に含まれる溶媒よりも顔料に対する溶解性が大きくなるように、pＨ調整物質を選択することが好ましい。 As the solvent used in the pigment solution that is the second fluid, the same solvent as the first fluid can be used. However, it is preferable to select a solvent having higher solubility in the pigment than the solvent contained in the first fluid. Further, the same substance as the first fluid can be added as the pH adjusting substance. It is preferable to select the pH adjusting substance so that the second fluid is more soluble in the pigment than the solvent contained in the first fluid.
　さらに、前記の第１流体ならびに第２流体に含まれる溶媒及びｐＨ調整物質の混合溶液（pＨ調整溶液）は、全ての物質が完全に溶け合った溶液状態であっても、懸濁状態であっても使用できる。 Furthermore, the mixed solution of the solvent and pH adjusting substance (pH adjusting solution) contained in the first fluid and the second fluid is in a suspended state even in a solution state in which all substances are completely dissolved. Can also be used.
　さらに、第１流体もしくは第２流体に、顔料の結晶型の制御や顔料の品質コントロールなどの目的のために有機溶剤を混合してもよい。有機溶剤としては公知のものが使用できる。また、有機溶剤以外にも、高分子ポリマー、ブロック共重合体等の分散剤、界面活性剤などを含んでもよい。 Furthermore, an organic solvent may be mixed with the first fluid or the second fluid for the purpose of controlling the crystal type of the pigment or controlling the quality of the pigment. Known organic solvents can be used. Further, in addition to the organic solvent, a dispersing agent such as a polymer, a block copolymer, a surfactant, and the like may be included.
　前記の各方法に用いられる顔料としては特に限定されないが、多環キノン系顔料、ペリレン系顔料、アゾ系顔料、インジゴ顔料、キナクリドン顔料、フタロシアニン顔料などの公知の有機系顔料が挙げられる。 The pigment used in each of the above methods is not particularly limited, and examples thereof include known organic pigments such as polycyclic quinone pigments, perylene pigments, azo pigments, indigo pigments, quinacridone pigments, and phthalocyanine pigments.
　また、顔料としては粒状固体、染料化合物のような顔料を含む。顔料の例として、無機の無彩色顔料、有機、無機の有彩色顔料があり、また、無色または淡色の顔料、金属光沢顔料等を使用してもよい。本発明のために、新規に合成した顔料を用いてもよい。以下に顔料の具体例を挙げる。 Also, pigments include particulate solids and pigments such as dye compounds. Examples of the pigment include inorganic achromatic pigments, organic and inorganic chromatic pigments, and colorless or light color pigments, metallic luster pigments, and the like may be used. For the present invention, a newly synthesized pigment may be used. Specific examples of the pigment are given below.
　黒色の顔料としては、例えば、以下のものを挙げることができる。即ち、Ｒａｖｅｎ１０６０ 、Ｒａｖｅｎ １０８０ 、Ｒａｖｅｎ １１７０ 、Ｒａｖｅｎ １２００ 、Ｒａｖｅｎ １２５０ 、Ｒａｖｅｎ １２５５ 、Ｒａｖｅｎ １５００ 、Ｒａｖｅｎ ２０００ 、Ｒａｖｅｎ ３５００ 、Ｒａｖｅｎ ５２５０ 、Ｒａｖｅｎ ５７５０ 、Ｒａｖｅｎ７０００ 、Ｒａｖｅｎ ５０００ ＵＬＴＲＡＩＩ 、Ｒａｖｅｎ １１９０ ＵＬＴＲＡＩＩ （以上、コロンビアン・カーボン社製）である。また、Ｂｌａｃｋ ＰｅａｒｌｓＬ 、Ｍｏｇｕｌ －Ｌ 、Ｒｅｇａｌ ４００Ｒ 、Ｒｅｇａｌ ６６０Ｒ 、Ｒｅｇａｌ ３３０Ｒ 、Ｍｏｎａｒｃｈ ８００ 、Ｍｏｎａｒｃｈ ８８０ 、Ｍｏｎａｒｃｈ ９００ 、Ｍｏｎａｒｃｈ １０００ 、Ｍｏｎａｒｃｈ １３００ 、Ｍｏｎａｒｃｈ １４００ （以上、キャボット社製）である。また、Ｃｏｌｏｒ Ｂｌａｃｋ ＦＷ１ 、Ｃｏｌｏｒ Ｂｌａｃｋ ＦＷ２ 、Ｃｏｌｏｒ Ｂｌａｃｋ ＦＷ２００ 、Ｃｏｌｏｒ Ｂｌａｃｋ １８ 、Ｃｏｌｏｒ Ｂｌａｃｋ Ｓ１６０ 、Ｃｏｌｏｒ Ｂｌａｃｋ Ｓ１７０ 、Ｓｐｅｃｉａｌ Ｂｌａｃｋ ４ ，Ｓｐｅｃｉａｌ Ｂｌａｃｋ ４Ａ ，Ｓｐｅｃｉａｌ Ｂｌａｃｋ ６ ，Ｐｒｉｎｔｅｘ ３５ ，Ｐｒｉｎｔｅｘ Ｕ ，Ｐｒｉｎｔｅｘ １４０Ｕ ，Ｐｒｉｎｔｅｘ Ｖ ，Ｐｒｉｎｔｅｘ １４０Ｖ （以上デグッサ社製）である。また、Ｎｏ．２５ 、Ｎｏ ．３３ 、Ｎｏ ．４０ 、Ｎｏ ．４７ 、Ｎｏ ．５２ 、Ｎｏ ．９００ 、Ｎｏ ．２３００ 、ＭＣＦ －８８ 、ＭＡ６００ 、ＭＡ７ 、ＭＡ８ 、ＭＡ１００ （以上三菱化学社製）等である。しかしこれらに限定されない。 Examples of black pigments include the following. Raven 1060 １０, Raven 1080, Raven 1170, Raven 1200, Raven 1250, Raven 1255, Raven 1500, Raven 2000, Raven 3500, Raven 5250, Raven 5250, Raven 5250 Ｒ Company-made). Also, Black PearlsL, Mogu -L, Regal 400R, Regal 660R, Regal 330R, Monarch 800, Monarch 880, Monarch 900, Monarch 1000, Monarch 1300, Monarch 1400, manufactured by Monarch Further, Color Black FW1, Color Black FW2, Color Black FW200, Color Black 18, Color Black S160, Color Black S170, Special Black 4, Special Black 4A, Special Black 6, Printex 35, Printex U, Printex 140U, Printex V, Printex 140V (manufactured by Degussa). No. 25, No. 33, No. 40, No. 47, No. 52, No. 900, No. 2,300 mm, MCF-88 mm, MA600 mm, MA7 mm, MA8 mm, MA100 mm (manufactured by Mitsubishi Chemical). However, it is not limited to these.
　シアン色の顔料としては、以下のものを挙げることができる。即ち、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｂｌｕｅ －１ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｂｌｕｅ －２ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｂｌｕｅ －３ である。また、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｂｌｕｅ －１５ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｂｌｕｅ －１５ ：２ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｂｌｕｅ －１５ ：３ 、Ｃ．Ｉ ．Ｐｉｇｍｅｎｔ Ｂｌｕｅ －１５ ：４ である。また、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｂｌｕｅ －１６ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｂｌｕｅ －２２ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｂｌｕｅ －６０ 等である。 Examples of cyan pigments include the following. That is, C. I. Pigment Blue -1, C. I. Pigment Blue -2, C. I. Pigment Blue -3. In addition, C. I. Pigment Blue -15, C. I. Pigment Blue -15: 2, C. I. Pigment Blue -15: 3, C.I. I. Pigment Blue -15: 4. In addition, C. I. Pigment Blue -16, C. I. Pigment Blue -22, C. I. Pigment Blue -60 and the like.
　マゼンタ色の顔料としては、以下ものを挙げることができる。即ち、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｒｅｄ －５ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｒｅｄ －７ 、Ｃ ．Ｉ ．ＰｉｇｍｅｎｔＲｅｄ －１２ である。また、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｒｅｄ －４８ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｒｅｄ －４８ ：１ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｒｅｄ －５７ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｒｅｄ －１１２ である。また、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｒｅｄ －１２２ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｒｅｄ －１２３ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｒｅｄ －１４６ 、Ｃ ．I.Ｐｉｇｍｅｎｔ Ｒｅｄ －１６８ である。また、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｒｅｄ －１８４ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｒｅｄ －２０２ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｒｅｄ －２０７ 等である。 Examples of magenta pigments include the following. That is, C. I. Pigment Red -5, C. I. Pigment Red -7, C. I. PigmentRed -12. In addition, C. I. Pigment Red -48, C. I. Pigment Red -48: 1, C. I. Pigment Red -57, C. I. Pigment Red -112. In addition, C. I. Pigment Red -122, C. I. Pigment Red -123, C. I. Pigment Red -146, C. I. Pigment Red -168. In addition, C. I. Pigment Red -184, C. I. Pigment Red -202, C. I. Pigment Red -207.
　黄色の顔料としては、以下のものを挙げることができる。即ち、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｙｅｌｌｏｗ －１２ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｙｅｌｌｏｗ －１３ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｙｅｌｌｏｗ －１４ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｙｅｌｌｏｗ －１６ である。また、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｙｅｌｌｏｗ －１７ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｙｅｌｌｏｗ －７４ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｙｅｌｌｏｗ －８３ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｙｅｌｌｏｗ －９３ である。また、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｙｅｌｌｏｗ －９５ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｙｅｌｌｏｗ －９７ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｙｅｌｌｏｗ－９８ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｙｅｌｌｏｗ －１１４ である。また、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｙｅｌｌｏｗ －１２８ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｙｅｌｌｏｗ －１２９ 、Ｃ．Ｉ ．Ｐｉｇｍｅｎｔ Ｙｅｌｌｏｗ －１５１ 、Ｃ ．Ｉ ．Ｐｉｇｍｅｎｔ Ｙｅｌｌｏｗ－１５４ 等である。 The following can be listed as yellow pigments. That is, C. I. Pigment Yellow -12, C. I. Pigment Yellow -13, C. I. Pigment Yellow -14, C. I. Pigment Yellow -16. In addition, C. I. Pigment Yellow -17, C. I. Pigment Yellow -74, C. I. Pigment Yellow -83, C. I. Pigment Yellow -93. In addition, C. I. Pigment Yellow -95, C. I. Pigment Yellow -97, C. I. Pigment Yellow-98, C. I. Pigment Yellow -114. In addition, C. I. Pigment Yellow -128, C. I. Pigment Yellow -129, C.I. I. Pigment Yellow 151, C. I. Pigment “Yellow-154”.
　さらに、前記の黒色、シアン色、マゼンタ色、黄色の顔料以外にも目的の色に応じて様々な顔料を用いる事ができる。代表的にＰｉｇｍｅｎｔ Ｖｉｏｌｅｔ －２３のような紫色の顔料やＰｉｇｍｅｎｔ Ｇｒｅｅｎ －７のような緑色の顔料、Ｐｉｇｍｅｎｔ Ｏｒａｎｇｅ －４３のような橙色の顔料などが挙げられるが、顔料としての色を呈するものであれば実施できる。 Furthermore, in addition to the black, cyan, magenta, and yellow pigments described above, various pigments can be used depending on the target color. Typical examples include purple pigments such as Pigment Violet -23, green pigments such as Pigment Green -7, and orange pigments such as Pigment Orange -43. Can be implemented.
　また、本発明においては顔料同様に染料を用いることもできる。例としては、Ｃ ．Ｉ ．ソルベントブルー，－３３ ，－３８ ，－４２ ，－４５ ，－５３ ，－６５ ，－６７ ，－７０ ，－１０４ ，－１１４ ，－１１５ ，－１３５ を挙げることができる。また、Ｃ ．Ｉ ．ソルベントレッド，－２５ ，－３１ ，－８６ ，－９２ ，－９７ ，－１１８ ，－１３２ ，－１６０ ，－１８６ ，－１８７ ，－２１９ を挙げることができる。また、Ｃ ．Ｉ ．ソルベントイエロー，－１ ，－４９ ，－６２ ，－７４ ，－７９ ，－８２ ，－８３ ，－８９ ，－９０ ，－１２０ ，－１２１ ，－１５１ ，－１５３ ，－１５４ 等を挙げることができる。 In the present invention, a dye can be used in the same manner as the pigment. As an example, C. I. Solvent Blue, -33, -38, -42, -45, -53, -65, -67, -70, -104, -114, -115, -135. In addition, C. I. Solvent Red, -25, -31, -86, -92, -97, -118, -132, -160, -186, -187, -219. In addition, C. I. Solvent Yellow, -1, -49, -62, -74, -79, -82, -83, -89, -90, -120, -121, -151, -153, -154, etc. .
　水溶性染料も使用することが出来る。例としては、Ｃ ．Ｉ ．ダイレクトブラック，－１７ ，－１９ ，－２２ ，－３２ ，－３８ ，－５１ ，－６２ ，－７１ ，－１０８ ，－１４６ ，－１５４ ；Ｃ ．Ｉ ．ダイレクトイエロー，－１２ ，－２４ ，－２６ ，－４４ ，－８６ ，－８７ ，－９８ ，－１００ ，－１３０ ，－１４２ ；Ｃ ．Ｉ ．ダイレクトレッド，－１ ，－４，－１３ ，－１７ ，－２３ ，－２８ ，－３１ ，－６２ ，－７９ ，－８１ ，－８３ ，－８９，－２２７ ，－２４０ ，－２４２ ，－２４３ ；Ｃ ．Ｉ ．ダイレクトブルー，－６ ，－２２，－２５ ，－７１ ，－７８ ，－８６ ，－９０ ，－１０６ ，－１９９ ；Ｃ ．Ｉ ．ダイレクトオレンジ，－３４ ，－３９ ，－４４ ，－４６ ，－６０ ；Ｃ ．Ｉ ．ダイレクトバイオレット，－４７ ，－４８ ；Ｃ ．Ｉ ．ダイレクトブラウン，－１０９ ；Ｃ ．Ｉ ．ダイレクトグリーン，－５９ 等の直接染料、Ｃ ．Ｉ ．アシッドブラック，－２ ，－７ ，－２４ ，－２６ ，－３１ ，－５２ ，－６３ ，－１１２ ，－１１８ ，－１６８ ，－１７２ ，－２０８ ；Ｃ ．Ｉ ．アシッドイエロー，－１１ ，－１７ ，－２３ ，－２５ ，－２９ ，－４２ ，－４９ ，－６１ ，－７１ ；Ｃ ．Ｉ ．アシッドレッド，－１ ，－６ ，－８ ，－３２ ，－３７ ，－５１ ，－５２ ，－８０ ，－８５ ，－８７ ，－９２ ，－９４ ，－１１５ ，－１８０ ，－２５４ ，－２５６ ，－２８９ ，－３１５，－３１７ ；Ｃ ．Ｉ ．アシッドブルー，－９ ，－２２ ，－４０ ，－５９ ，－９３ ，－１０２ ，－１０４ ，－１１３ ，－１１７ ，－１２０ ，－１６７ ，－２２９ ，－２３４ ，－２５４ ；Ｃ ．Ｉ ．アシッドオレンジ，－７ ，－１９ ；Ｃ ．Ｉ ．アシッドバイオレット，－４９等の酸性染料、Ｃ ．Ｉ ．リアクティブブラック，－１ ，－５ ，－８ ，－１３ ，－１４ ，－２３ ，－３１，－３４ ，－３９ ；Ｃ ．Ｉ ．リアクティブイエロー，－２ ，－３ ，－１３ ，－１５ ，－１７ ，－１８ ，－２３ ，－２４ ，－３７ ，－４２ ，－５７ ，－５８ ，－６４ ，－７５ ，－７６ ，－７７ ，－７９ ，－８１ ，－８４ ，－８５ ，－８７ ，－８８ ，－９１ ，－９２ ，－９３ ，－９５ ，－１０２ ，－１１１ ，－１１５ ，－１１６ ，－１３０ ，－１３１ ，－１３２，－１３３ ，－１３５ ，－１３７ ，－１３９ ，－１４０ ，－１４２ ，－１４３ ，－１４４，－１４５ ，－１４６ ，－１４７ ，－１４８ ，－１５１ ，－１６２ ，－１６３ ；Ｃ ．Ｉ ．リアクティブレッド，－３ ，－１３ ，－１６ ，－２１ ，－２２ ，－２３ ，－２４ ，－２９，－３１ ，－３３ ，－３５ ，－４５ ，－４９ ，－５５ ，－６３ ，－８５ ，－１０６ ，－１０９ ，－１１１ ，－１１２ ，－１１３ ，－１１４ ，－１１８ ，－１２６ ，－１２８ ，－１３０ ，－１３１ ，－１４１ ，－１５１ ，－１７０ ，－１７１ ，－１７４ ，－１７６ ，－１７７ ，－１８３ ，－１８４ ，－１８６ ，－１８７ ，－１８８ ，－１９０ ，－１９３ ，－１９４ ，－１９５ ，－１９６ ，－２００ ，－２０１ ，－２０２ ，－２０４ ，－２０６ ，－２１８ ，－２２１ ；Ｃ ．Ｉ ．リアクティブブルー，－２ ，－３ ，－５ ，－８ ，－１０ ，－１３ ，－１４ ，－１５ ，－１８ ，－１９ ，－２１ ，－２５ ，－２７ ，－２８ ，－３８ ，－３９ ，－４０ ，－４１ ，－４９ ，－５２ ，－６３ ，－７１ ，－７２ ，－７４ ，－７５ ，－７７ ，－７８ ，－７９ ，－８９ ，－１００ ，－１０１ ，－１０４ ，－１０５ ，－１１９ ，－１２２ ，－１４７ ，－１５８ ，－１６０ ，－１６２ ，－１６６ ，－１６９ ，－１７０ ，－１７１ ，－１７２ ，－１７３ ，－１７４ ，－１７６ ，－１７９ ，－１８４ ，－１９０ ，－１９１ ，－１９４ ，－１９５ ，－１９８ ，－２０４ ，－２１１ ，－２１６ ，－２１７ ；Ｃ．Ｉ ．リアクティブオレンジ，－５ ，－７ ，－１１ ，－１２ ，－１３ ，－１５ ，－１６ ，－３５ ，－４５ ，－４６ ，－５６ ，－６２ ，－７０ ，－７２ ，－７４ ，－８２ ，－８４ ，－８７ ，－９１ ，－９２ ，－９３ ，－９５ ，－９７ ，－９９ ；Ｃ ．Ｉ ．リアクティブバイオレット，－１ ，－４ ，－５ ，－６ ，－２２ ，－２４ ，－３３ ，－３６ ，－３８ ；Ｃ ．Ｉ．リアクティブグリーン，－５ ，－８ ，－１２ ，－１５ ，－１９ ，－２３ ；Ｃ ．Ｉ ．リアクティブブラウン，－２ ，－７ ，－８ ，－９ ，－１１ ，－１６ ，－１７ ，－１８ ，－２１，－２４ ，－２６ ，－３１ ，－３２ ，－３３ 等の反応染料；Ｃ ．Ｉ ．ベーシックブラック，－２ ；Ｃ ．Ｉ ．ベーシックレッド，－１ ，－２ ，－９ ，－１２ ，－１３ ，－１４ ，－２７ ；Ｃ ．Ｉ ．ベーシックブルー，－１ ，－３ ，－５ ，－７，－９ ，－２４ ，－２５ ，－２６ ，－２８ ，－２９ ；Ｃ ．Ｉ ．ベーシックバイオレット，－７ ，－１４ ，－２７ ；Ｃ ．Ｉ ．フードブラック，－１ ，－２ 等が挙げられる。 Water-soluble dyes can also be used. As an example, C. I. Direct black, -17, -19, -22, -32, -38, -51, -62, -71, -108, -146, -154; C. I. Direct Yellow, -12, -24, -26, -44, -86, -87, -98, -100, -130, -142; C. I. Direct Red, -1, -4, -13, -17, -23, -28, -31, -62, -79, -81, -83, -89, -227, -240, -242, -243 C. I. Direct Blue, -6, -22, -25, -71, -78, -86, -90, -106, -199; C. I. Direct orange, -34, -39, -44, -46, -60; C. I. Direct violet, -47, -48; C. I. Direct Brown, -109; C. I. Direct green, direct dyes such as -59, C. I. Acid Black, -2, -7, -24, -26, -31, -52, -63, -112, -118, -168, -172, -208; C. I. Acid Yellow, -11, -17, -23, -25, -29, -42, -49, -61, -71; C. I. Acid Red, -1mm, -6mm, -8mm, -32mm, -37mm, -51mm, -52mm, -80mm, -85mm, -87mm, -92mm, -94mm, -115mm, -180mm, -254mm, -256 , -289, -315, -317; C. I. Acid Blue, -9, -22, -40, -59, -93, -102, -104, -113, -117, -120, -167, -229, -234, -254; C. I. Acid Orange, -7, -19; C. I. Acid violet, acidic dyes such as −49, C. I. Reactive Black, -1, -5, -8, -13, -14, -23, 31-1, -34, -39; C. I. Reactive Yellow, -2, -3, -13, -15, -17, -18, -23, -24, -37, -42, -57, -58, -64, -75, -76,- 77, -79, -81, -84, -85, -87, -88, -91, -92, -93, -95, -102, -111, -115, -116, -130, -131, -132, -133, -135, -137, -139, -140, -142, -143, -144, -145, -146, -147, -148, -151, -162, -163; I. Reactive Red, -3mm, -13mm, -16mm, -21mm, -22mm, -23mm, -24mm, -29, -31mm, -33mm, -35mm, -45mm, -49mm, -55mm, -63mm,- 85, -106, -109, -111, -112, -113, -114, -118, -126, -128, -130, -131, -141, -151, -170, -171, -174, -176, -177, -183, -184, -186, -187, -188, -190, -193, -194, -195, -196, -200, -201, -202, -204, -206 , -218, -221; C. I. Reactive Blue, -2, -3, -5, -8, -10, -13, -14, -15, -18, -19, -21, -25, -27, -28, -38,- 39 mm, -40 mm, -41 mm, -49 mm, -52 mm, -63 mm, -71 mm, -72 mm, -74 mm, -75 mm, -77 mm, -78 mm, -79 mm, -89 mm, -100 mm, -101 mm, -104 mm, -105, -119, -122, -147, -158, -160, -162, -166, -169, -170, -171, -172, -173, -174, -176, -179, -184 , -190, -191, -194, -195, -198, -204, -211, -216, -217; I. Reactive Orange, -5, -7, -11, -12, -13, -15, -16, -35, -45, -46, -56, -62, -70, -72, -74,- 82, -84, -87, -91, -92, -93, -95, -97, -99; C. I. Reactive violet, -1, -4, -5, -6, -22, -24, -33, -36, -38; C. I. Reactive Green, -5, -8, -12, -15, -19, -23; C. I. Reactive dyes such as reactive brown, -2, -7, -8, -9, -11, -16, -17, -18, -21, -24, -26, -31, -32, -33; C. I. Basic Black, -2; C. I. Basic Red, -1, -2, -9, -12, -13, -14, -27; C. I. Basic Blue, -1, -3, -5, -7, -9, -24, -25, -26, -28, -29; C. I. Basic violet, -7, -14, -27; C. I. Food black, -1, -2, etc. are mentioned.
　使用しうる染料は、公知のものでも新規のものでもよい。例えば以下に述べるような直接染料、酸性染料、塩基性染料、反応染料、食品用色素の水溶性染料、脂溶性（油溶性）染料又は、分散染料の不溶性色素を用いることができる。これらは、固体化した状態で使用しても良い。この点では好ましくは、例えば、油溶性染料を使用し得る。 Dyes that can be used may be known or new ones. For example, direct dyes, acid dyes, basic dyes, reactive dyes, water-soluble dyes for food coloring, fat-soluble (oil-soluble) dyes, or insoluble dyes of disperse dyes as described below can be used. These may be used in a solid state. In this respect, for example, oil-soluble dyes may be used.
　本発明で言う油溶性染料とは、有機溶媒に溶解する染料を言い、脂溶性染料とも呼ばれる。 In the present invention, the oil-soluble dye refers to a dye that dissolves in an organic solvent, and is also referred to as a fat-soluble dye.
　界面活性剤及び分散剤としては顔料の分散用途に用いられる様々な市販品を使用できる。特に限定されないが、例えばネオゲンＲ－Ｋ（第一工業製薬）のようなドデシルベンゼンスルホン酸系や、ソルスパース２００００ 、ソルスパース２４０００ 、ソルスパース２６０００ 、ソルスパース２７０００ 、ソルスパース２８０００ 、ソルスパース４１０９０ （以上、アビシア社製）、ディスパービック１６０ 、ディスパービック１６１ 、ディスパービック１６２ 、ディスパービック１６３ 、ディスパービック１６６ 、ディスパービック１７０ 、ディスパービック１８０ 、ディスパービック１８１ 、ディスパービック１８２ 、ディスパービック－１８３ 、ディスパービック１８４ 、ディスパービック１９０ 、ディスパービック１９１ 、ディスパービック１９２ 、ディスパービック－２０００ 、ディスパービック－２００１ （以上、ビックケミー社製）、ポリマー１ ００ 、ポリマー１２０ 、ポリマー１５０ 、ポリマー４００ 、ポリマー４０１ 、ポリマー４０２ 、ポリマー４０３ 、ポリマー４５０ 、ポリマー４５１ 、ポリマー４５２ 、ポリマー４ ５３ 、ＥＦＫＡ －４６ 、ＥＦＫＡ －４７ 、ＥＦＫＡ －４８ 、ＥＦＫＡ －４９ 、ＥＦＫＡ－１５０１ 、ＥＦＫＡ －１５０２ 、ＥＦＫＡ －４５４０ 、ＥＦＫＡ －４５５０ （以上、ＥＦ ＫＡ ケミカル社製）、フローレンＤＯＰＡ －１５８ 、フローレンＤＯＰＡ －２２ 、フローレンＤＯＰＡ －１７ 、フローレンＧ －７００ 、フローレンＴＧ －７２０Ｗ 、フローレン－７３０Ｗ 、フローレン－７４０Ｗ 、フローレン－７４５Ｗ 、（以上、共栄社化学社製）、アジスパーＰＡ１１１ 、アジスパーＰＢ７１１ 、アジスパーＰＢ８１１ 、アジスパーＰＢ ８２１ 、アジスパーＰＷ９１１ （以上、味の素社製）、ジョンクリル６７８ 、ジョンクリル６７９ 、ジョンクリル６２ （以上、ジョンソンポリマー社製）等を挙げることができる。これらは単独で使用してもよく、２種以上を併用してもよい。 As the surfactant and dispersant, various commercially available products used for pigment dispersion can be used. Although not particularly limited, for example, dodecylbenzene sulfonic acid type such as Neogen RK (Daiichi Kogyo Seiyaku), Solsperse 20000２０, Solsperse 24000, Solsperse 26000, Solsperse 27000, Solsperse 28000, Solsperse 41090 (above, manufactured by Abyssia) , Disperbic 160, Disperbic 161 ビ, Disperbic 162, Disperbic 163, Disperbic 166, Disperbic 170, Disperbic 180, Disperbic 181, Disperbic 182, Disperbic-183, Disperbic 184, Disperbic 190, Dispersic 191, Dispersic 192, Dispersic-2000, Disper -2001 (above, manufactured by BYK Chemie), Polymer 1 ポ リ マ ー 00, Polymer 120, Polymer 150, Polymer 400, Polymer 401, Polymer 402, Polymer 403, Polymer 450, Polymer 451, Polymer 452, Polymer 4 53, EFKA -46 , EFKA -47, EFKA -48, EFKA -49, EFKA-1501, EFKA -1502, EFKA -4540, EFKA -4550 (above, manufactured by EF KA Chemical Co., Ltd.), FLOREN DOPA -158, FLOREN DOPA PA -22 -17, Floren G -700, Floren TG -720W, Florene-730W, Florene-740W, Floren-745W, (Kyoeisha Chemical Co., Ltd.) ), Addispar PA111, Addisper PB711, Addisper PB811, Addisper PB 821, Addispar PW911 (above, manufactured by Ajinomoto Co., Inc.), Jonkrill 678, Jonkrill 679, and Johnkrill 62 (above, made by Johnson Polymer Co., Ltd.) . These may be used alone or in combination of two or more.
　また本発明においてブロック共重合体として、具体的な例として以下を挙げることができる。即ち、アクリル系、メタクリル系ブロック共重合体、ポリスチレンと他の付加重合系または縮合重合系のブロック共重合体、ポリオキシエチレン、ポリオキシアルキレンのブロックを有するブロック共重合体等である。そして、従来から知られているブロック共重合体を用いることもできる。本発明に用いられるブロック共重合体は両親媒性であることが好ましい。具体的に好ましい形としては、疎水セグメントと有機酸あるいはそのイオン性塩ユニットを持つ親水セグメントからなるジブロック共重合体を挙げることができる。また、疎水セグメントと有機酸あるいはそのイオン性塩ユニットを持つ親水セグメントとさらに別のセグメントを有するトリブロック共重合体が好ましく用いられる。トリブロックの場合、疎水セグメント、非イオン性の親水セグメント、有機酸あるいはそのイオン性塩ユニットを持つ親水セグメントである形が好ましく用いられ、内包状態の安定化の意味でも好ましい。例えば前述したトリブロック共重合体を使用して、顔料物質と、溶媒として水を使用して分散液を調製すると、顔料をトリブロック共重合体が形成するミセル中に内包させることが可能であり、そのように顔料内包型のインク組成物を形成することも可能となる。また、その分散組成物の粒子の粒子径も非常に揃った均一なものとすることも可能である。さらにはその分散状態を極めて安定なものとすることも可能である。これらの処理を、前記装置を用いて行うと顔料微粒子の粒子径も非常に揃って均一性がさらに向上する。 In the present invention, specific examples of the block copolymer include the following. That is, acrylic, methacrylic block copolymers, polystyrene and other addition polymerization or condensation polymerization block copolymers, block copolymers having polyoxyethylene and polyoxyalkylene blocks, and the like. A conventionally known block copolymer can also be used. The block copolymer used in the present invention is preferably amphiphilic. As a particularly preferred form, there can be mentioned a diblock copolymer comprising a hydrophobic segment and a hydrophilic segment having an organic acid or an ionic salt unit thereof. Further, a triblock copolymer having a hydrophobic segment, a hydrophilic segment having an organic acid or an ionic salt unit thereof, and another segment is preferably used. In the case of a triblock, a form that is a hydrophobic segment, a nonionic hydrophilic segment, a hydrophilic segment having an organic acid or an ionic salt unit thereof is preferably used, and is also preferable in terms of stabilization of the inclusion state. For example, when the above-described triblock copolymer is used to prepare a dispersion using a pigment substance and water as a solvent, the pigment can be encapsulated in micelles formed by the triblock copolymer. Thus, it is possible to form a pigment-encapsulated ink composition. In addition, the particle size of the particles of the dispersion composition can also be made very uniform and uniform. Furthermore, the dispersion state can be made extremely stable. When these treatments are carried out using the above apparatus, the particle diameters of the pigment fine particles are very uniform and the uniformity is further improved.
　また前記の各方法以外にも、前記装置を用いた顔料微粒子の製造方法として、薄膜流体中で顔料を直接合成してもよい。一例として銅フタロシアニンの合成例の場合には、無水フタル酸またはその誘導体、銅またはその化合物、尿素またはその誘導体及び触媒を有機溶媒中またはその不存在下において反応させる事で、銅フタロシアニン顔料を得る方法に代表されるような、顔料を種々の反応を用いて直接合成しても良い。これにより、これまでの方法では、合成工程によって出来た粗大な顔料微粒子を粉砕する工程が必要であったが、これが必要なくなる事や、さらに粉砕工程が必要な場合にも、運転条件によって薄膜流体中にせん断力を与え、粉砕工程を含むことができる。 In addition to the above methods, as a method for producing pigment fine particles using the apparatus, a pigment may be directly synthesized in a thin film fluid. As an example, in the case of the synthesis example of copper phthalocyanine, a copper phthalocyanine pigment is obtained by reacting phthalic anhydride or a derivative thereof, copper or a compound thereof, urea or a derivative thereof and a catalyst in an organic solvent or in the absence thereof. Pigments may be directly synthesized using various reactions, as represented by the method. As a result, in the conventional methods, a process for pulverizing coarse pigment fine particles produced by the synthesis process is necessary. A shearing force can be applied therein, and a grinding step can be included.
　本発明においては、混合流路中での混合は、層流支配下で行なうこともできるし、乱流支配下で行なうこともできる。 In the present invention, mixing in the mixing channel can be performed under laminar flow control or turbulent flow control.
　さらに、処理用面間を加熱、冷却したり、あるいは処理用面間にマイクロウェーブを照射することも可能である。また処理用面間に紫外線（ＵＶ）を照射したり、また処理用面間に超音波エネルギーを与えてもかまわない。特に、第１処理用面１と第２処理用面２とで温度差を設けた場合は、薄膜流体中で対流を発生させることができるため、これにより反応を促進させることができるという利点がある。 Furthermore, it is possible to heat and cool the space between the processing surfaces, or to irradiate microwaves between the processing surfaces. Further, ultraviolet rays (UV) may be irradiated between the processing surfaces, or ultrasonic energy may be applied between the processing surfaces. In particular, when a temperature difference is provided between the first processing surface 1 and the second processing surface 2, convection can be generated in the thin film fluid, which has the advantage that the reaction can be promoted. is there.
　より具体的に、加熱、冷却については、例えば各処理用部１０，２０の少なくとも一方或いは双方にヒーターや熱媒、冷媒を通すジャケットを設けることにより、薄膜流体を加熱、冷却できるようにする。あるいは、各処理用部１０、２０の少なくとも一方或いは双方にマイクロウェーブを照射する為の、マグネトロンなどのマイクロ波発生装置を備えることにより、処理流体の加熱、反応促進を行う。また、紫外線（ＵＶ）を照射することについては、例えば各処理用部１０，２０の少なくとも一方或いは双方に紫外線を照射するランプなどの素子を設け、対応する処理用面から薄膜流体に紫外線（ＵＶ）を照射できるようにする。また、超音波エネルギーを与えることについては、例えば各処理用部１０，２０の少なくとも一方或いは双方に超音波発振体を設けることができるし、処理用面間での混合・反応を超音波雰囲気の容器内で行っても実施できる。 More specifically, with regard to heating and cooling, for example, a jacket through which a heater, a heat medium, and a refrigerant are passed is provided in at least one or both of the processing units 10 and 20, so that the thin film fluid can be heated and cooled. Alternatively, the processing fluid is heated and the reaction is accelerated by providing a microwave generator such as a magnetron for irradiating at least one or both of the processing units 10 and 20 with microwaves. In addition, for irradiating ultraviolet rays (UV), for example, an element such as a lamp for irradiating ultraviolet rays is provided on at least one or both of the processing units 10 and 20, and ultraviolet rays (UV) are applied to the thin film fluid from the corresponding processing surfaces. ) Can be irradiated. In addition, regarding the application of ultrasonic energy, for example, at least one or both of the processing units 10 and 20 can be provided with an ultrasonic oscillator, and mixing and reaction between the processing surfaces can be performed in an ultrasonic atmosphere. It can also be carried out in a container.
　また、前記析出を減圧または真空状態を確保できる容器内で行い、少なくとも処理後流体が吐出される２次側を減圧または真空状態とする事で、析出反応中に発生するガス並びに前記流体中に含まれるガスの脱気、もしくは前記流体の脱溶剤が行える。それにより、顔料微粒子析出とほぼ同時に脱溶剤処理を行う場合にも、処理用面間で析出した顔料微粒子を含む流体が、処理用面より噴霧状態で吐出するため、その流体の表面積が増大し、脱溶剤効率が非常に高い。そのため、これまでよりも簡単に、実質１工程で顔料微粒子作製処理と脱溶剤処理とが行える。 Further, the deposition is performed in a container capable of securing a reduced pressure or a vacuum state, and at least the secondary side from which the fluid is discharged after the processing is set to a reduced pressure or a vacuum state, whereby the gas generated during the precipitation reaction and the fluid are contained in the fluid. The contained gas can be degassed or the fluid can be desolvated. As a result, even when the solvent removal treatment is performed almost simultaneously with the pigment fine particle deposition, the fluid containing the pigment fine particles deposited between the processing surfaces is ejected in a sprayed state from the processing surfaces, so the surface area of the fluid increases. The solvent removal efficiency is very high. Therefore, the pigment fine particle preparation process and the solvent removal process can be performed in substantially one step more easily than before.
　また前述のように、第１導入部ｄ１、第２導入部ｄ２以外に第３導入部ｄ３を処理装置に設けることもできるが、この場合にあっては、例えば前記のアシッドペースティング法では、各導入部から、水又は有機溶媒を含む溶液、顔料を溶解した酸を含む流体、顔料の結晶型の制御や顔料の品質コントロール等の目的のための有機溶剤等をそれぞれ別々に処理装置に導入することが可能である。また、pＨ調整による場合にあっては、各導入部から、pＨを変化させる顔料析出用溶液、顔料溶液を含む流体、顔料の結晶型の制御や顔料の品質コントロール等の目的のための有機溶剤等をそれぞれ別々に処理装置に導入することが可能である。そうすると、各溶液の濃度や圧力を個々に管理することができ、顔料微粒子が生成する反応をより精密に制御することができる。第４以上の導入部を設けた場合も同様であって、このように処理装置へ導入する流体を細分化できる。 In addition to the first introduction part d1 and the second introduction part d2, a third introduction part d3 can be provided in the processing apparatus as described above. In this case, for example, in the acid pasting method, From each introduction part, a solution containing water or an organic solvent, a fluid containing an acid in which the pigment is dissolved, an organic solvent for the purpose of controlling the crystal form of the pigment and controlling the quality of the pigment, etc. are separately introduced into the processing apparatus. Is possible. In addition, in the case of pH adjustment, from each introduction part, a pigment precipitation solution for changing the pH, a fluid containing the pigment solution, an organic solvent for the purpose of controlling the crystal form of the pigment and controlling the quality of the pigment, etc. Etc. can be separately introduced into the processing apparatus. If it does so, the density | concentration and pressure of each solution can be managed separately, and the reaction which pigment fine particles produce | generate can be controlled more precisely. The same applies to the case where the fourth or more introduction portions are provided, and the fluid to be introduced into the processing apparatus can be subdivided in this way.
　本発明に用いる前記装置は、その薄膜流体のレイノルズ数を自由に変化させる事が可能であるため、粒子径、粒子形状、結晶型など、目的に応じて単分散で再分散性の良い顔料微粒子が作製出来る。しかもその自己排出性により、析出を伴う反応の場合であっても生成物の詰まりも無く、大きな圧力を必要としない。ゆえに、安定的に顔料微粒子を作製でき、また安全性に優れ、不純物の混入もほとんど無く、洗浄性も良い。さらに目的の生産量に応じてスケールアップ可能であるため、その生産性も高い顔料微粒子の製造方法を提供可能である。 Since the apparatus used in the present invention can freely change the Reynolds number of the thin film fluid, the fine particles of the pigment are monodispersed and have good redispersibility according to the purpose, such as particle diameter, particle shape, crystal type, etc. Can be made. Moreover, due to its self-discharging properties, there is no clogging of the product even in the case of a reaction involving precipitation, and a large pressure is not required. Therefore, pigment fine particles can be stably produced, and are excellent in safety, hardly contaminated with impurities, and have good cleaning properties. Furthermore, since it can be scaled up according to the target production volume, it is possible to provide a method for producing pigment fine particles with high productivity.
　次に述べる生体摂取物微粒子の析出反応が、接近・離反可能に互いに対向して配設され、少なくとも一方が他方に対して回転する処理用面１，２の間で強制的に均一混合しながら起こる。生体摂取物微粒子の粒子径や単分散度、又は結晶型の制御は、処理用面１，２の回転数や処理用面１，２間の距離、及び、薄膜流体の流速や温度又は原料濃度等を変えることにより調節することができる。この点は、特許４４１９１５７等において、本願出願人が指摘している通りであり、本願出願人は、析出ステップに重点をおいて、回転数、流速、処理用面間の距離を調整することによって、目的の物性や性能を有する微粒子の製造に取り組んできた。ところが、溶解ステップの調整、特に、攪拌エネルギーの増減によって、析出ステップに送られる流体の溶解の状態を調整することにて、析出ステップで得られる微粒子の結晶化度や結晶型を制御し得ることを知見して、本発明を完成したものである。これによって、析出ステップの条件を固定したまま、溶解ステップの条件を変更するだけで、微粒子の結晶化度や結晶型を変化させ、目的の微粒子の性状や性能を得るこができたり、溶解ステップと析出ステップとの両方の条件を変化させることで、目的の微粒子の性状や性能を、よりダイナミックに変更することができるようになったものである。 The following precipitation reaction of biologically ingested particulates is arranged so as to be able to approach and separate from each other, and at least one of them is uniformly mixed between the processing surfaces 1 and 2 rotating with respect to the other. Occur. Control of the particle size, monodispersity, or crystal type of fine particles in the body intake is controlled by the rotational speed of the processing surfaces 1 and 2, the distance between the processing surfaces 1 and 2, and the flow velocity, temperature, or raw material concentration of the thin film fluid. It can be adjusted by changing etc. This point is as pointed out by the present applicant in Patent 4419157, etc., and the present applicant emphasizes the precipitation step and adjusts the rotation speed, flow rate, and distance between the processing surfaces. We have been working on the production of fine particles with the desired physical properties and performance. However, it is possible to control the crystallinity and crystal form of the fine particles obtained in the precipitation step by adjusting the dissolution step, particularly by adjusting the dissolution state of the fluid sent to the precipitation step by increasing or decreasing the stirring energy. Thus, the present invention has been completed. This makes it possible to change the crystallinity and crystal form of the microparticles by changing the conditions of the dissolution step while fixing the conditions of the precipitation step, and to obtain the properties and performance of the target microparticles. By changing the conditions of both the precipitation step and the precipitation step, the properties and performance of the target fine particles can be changed more dynamically.
　以下、前記の装置を用いて行う、生体摂取物微粒子の製造方法の具体的な態様について説明する。ここでは、溶解度の変化によって生体摂取物微粒子を析出させる方法について述べるが、中和反応やｐＨ変化により生体摂取物を析出させる方法であってもよい。 Hereinafter, a specific aspect of the method for producing biologically ingested fine particles performed using the above-described apparatus will be described. Here, although the method of depositing biologically ingested fine particles by a change in solubility is described, a method of precipitating biologically ingested materials by a neutralization reaction or a pH change may be used.
　前記に説明した装置の処理用面の間に形成される薄膜流体中で、微粒子化する対象物質である生体摂取物微粒子原料を少なくとも１種類溶解している第１溶媒を含む溶液と、前記生体摂取物微粒子原料に対して第１溶媒よりも溶解度の低い第２溶媒となりうる溶媒を混合させ、生体摂取物微粒子を析出させる。 A solution containing a first solvent in which at least one biological ingested particulate raw material that is a target substance to be microparticulated is dissolved in a thin film fluid formed between the processing surfaces of the apparatus described above; The ingestible particulate raw material is mixed with a solvent that can be a second solvent having a lower solubility than the first solvent to precipitate the ingested particulate matter.
　前記の生体摂取物には薬物が含まれる。この発明は、多種多様な薬物で実施できる。薬物は、実質的に純粋な状態で存在する有機物質が好ましい。薬物は、少なくとも一種の溶媒に低い溶解性で分散可能であり、少なくとも一種の溶媒に可溶である必要がある。低い溶解性とは、薬物が処理温度（例えば、室温）で溶媒（例えば、水）に約１０ｍｇ／ｍＬ未満、好ましくは約１ｍｇ／ｍＬ未満の溶解性を有することを意味する。また、ここで可溶とは１０ｍｇ／ｍＬ以上に溶解することを意味する。なお、必要に応じて溶媒を加温または冷却することも可能である。また、分散剤（界面活性剤）や水溶性高分子、安定剤、保存剤、ｐＨ調整剤、等張化剤等を必要に応じて、第１溶媒もしくは第２溶媒、あるいはその両方にあらかじめ添加しておくと良い。 The aforementioned biological intake contains a drug. The invention can be practiced with a wide variety of drugs. The drug is preferably an organic substance that exists in a substantially pure state. The drug must be dispersible with low solubility in at least one solvent and must be soluble in at least one solvent. Low solubility means that the drug has a solubility of less than about 10 mg / mL, preferably less than about 1 mg / mL in a solvent (eg, water) at the processing temperature (eg, room temperature). Further, here, the term “soluble” means to dissolve at 10 mg / mL or more. In addition, it is also possible to heat or cool a solvent as needed. In addition, a dispersant (surfactant), a water-soluble polymer, a stabilizer, a preservative, a pH adjuster, an isotonic agent, etc. are added in advance to the first solvent or the second solvent, or both, as necessary. It is good to keep.
　適当な薬物は、例えば、鎮痛薬、抗炎症薬、駆虫薬、抗不整脈薬、抗生物質（ペニシリン類を含む）、抗凝固薬、抗降圧薬、抗糖尿病薬、抗てんかん薬、抗ヒスタミン薬、抗悪性腫瘍薬、抗肥満薬、食欲抑制薬、降圧薬、抗ムスカリン薬、抗ミコバクテリア薬、抗新生物薬、免疫抑制薬、抗甲状腺薬、抗菌薬、抗ウイルス薬、不安解消薬（催眠薬および神経弛緩薬）、アストリンゼント、アドレナリン性β受容体遮断薬、血液製剤および代用血漿、心筋変性力薬、コントラスト媒質、コルチコステロイド、咳抑制薬（去痰薬および粘液破壊薬）、診断薬、診断像形成薬、利尿薬、ドーパミン作用薬（抗パーキンソン氏病薬）、止血薬、免疫薬、リピッド調節薬、筋肉弛緩薬、副交感神経刺激興奮薬、副甲状腺カルシトニンおよびビホスホネート類、プロスタグランジン、放射性医薬、性ホルモン（ステロイド類を含む）、抗アレルギー薬、興奮薬および食欲減退物質、交感神経興奮薬、甲状腺薬、血管拡張剤およびキサンチン類、白内障治療剤、副腎皮質ホルモン剤、を含む各種既知薬物類から選ぶことができる。好ましい薬物としては、水に低溶解度で経口投与および注射剤を意図するものが挙げられる。これらのクラスの薬物類の記載および各クラスに含まれるリストは、「Ｍａｒｔｉｎｄａｌｅ， Ｔｈｅ Ｅｘｔｒａ Ｐｈａｒｍａｃｏｐｏｅｉａ ， 第２９版、Ｔｈｅ Ｐｈａｒａｃｅｕｔｉｃａｌ Ｐｒｅｓｓ，Ｌｏｎｄｏｎ，１９８９ 」に見い出すことができる。これらの薬物は市販されており、または当該技術分野で既知の方法で製造できる。 Suitable drugs include, for example, analgesics, anti-inflammatory drugs, anthelmintic drugs, antiarrhythmic drugs, antibiotics (including penicillins), anticoagulants, antihypertensive drugs, antidiabetic drugs, antiepileptic drugs, antihistamines, Antineoplastic, anti-obesity, appetite suppressant, antihypertensive, antimuscarinic, antimycobacterial, antineoplastic, immunosuppressive, antithyroid, antibacterial, antiviral, anxiolytic (hypnotic Drugs and neuroleptics), astrinsents, adrenergic beta-receptor blockers, blood products and plasma substitutes, myocardial degenerative drugs, contrast media, corticosteroids, cough suppressants (descendants and mucus destroyers), diagnostic agents, Diagnostic imaging agents, diuretics, dopamine agonists (anti-Parkinson's disease drugs), hemostatic agents, immune agents, lipid modulators, muscle relaxants, parasympathomimetic stimulants, parathyroid calcitonin and biphosphone Tomatoes, prostaglandins, radiopharmaceuticals, sex hormones (including steroids), antiallergic drugs, stimulants and anorexic substances, sympathomimetics, thyroid drugs, vasodilators and xanthines, cataract treatments, adrenal glands It can be selected from various known drugs including corticosteroids. Preferred drugs include those intended for oral administration and injection with low solubility in water. A description of these classes of drugs and the list contained in each class can be found in “Martindale, The Extra Pharmacopoeia, 29th edition, The ｈ Pharmaceutical Press, London, 1989”. These drugs are commercially available or can be prepared by methods known in the art.
　この発明を実施する上で有用な薬物の具体例としては、１７－α－プレグノ－２，４－ジエン－２０－イノ－〔２，３－ｄ〕－イソキサゾール－１７－オール（ダナゾール）、タクロリムス水和物、プロゲステロン、トラニラスト、ベンズブロマロン、メフェナム酸、〔６－メトキシ－４－（１－メチルエチル）－３－オキソ－１，２－ベンズイソチアゾール－２（３Ｈ）－イル〕メチル２，６－ジクロロベンゾエート１，１－ジオキシド（ＷＩＮ ６３，３９４）、３－アミノ－１，２，４－ベンゾトリアジン－１，４－ジオキシド（ＷＩＮ ５９，０７５）、ピポサルファム、ピポサルファン、カンプトテシン、アセトミノフェン、アセチルサリチル酸、アミオダロン、コレスチフミン、コレスチポール、クロモリンナトリウム、アルブテロール、スクラルフェート、スルファサラジン、ミノキシジル、テンパゼパム、アルプラゾラム、プロポキシフェン、オーラノフィン、エリスロマイシン、サイクロスポリン、アシクロビア、ガンシクロビア、エトポサイド、メファラン、メトトリキセート、ミノキサントロン、ダウノルビシン、ドキソルビシン、メゲステロール、タモキシフェン、メドロキシプロゲステロン、ナイスタチン、テルブタリン、アンホテリシンＢ、アスピリン、イブプロフェン、ナプロキセン、インドメタシン、ジクロフェナック、ケトプロフェン、フルビプロフェン、ジフルニサル、エチル－３，５－ジアセトアミド－２，４，６－トリヨードベンゾエート（ＷＩＮ ８８８３）、エチル（３，５－ビス（アセチルアミノ）－２，４，６－トリヨードベンゾイルオキシ）アセテート（ＷＩＮ １２，９０１）およびエチル－２－（３，５－ビス（アセチルアミノ）－２，４，６－トリヨードベンゾイルオキシ）アセテート（ＷＩＮ １６，３１８）が代表的なものとして挙げられる。 Specific examples of drugs useful in the practice of this invention include 17-α-pregno-2,4-diene-20-ino- [2,3-d] -isoxazol-17-ol (danazol), tacrolimus Hydrate, progesterone, tranilast, benzbromarone, mefenamic acid, [6-methoxy-4- (1-methylethyl) -3-oxo-1,2-benzisothiazol-2 (3H) -yl] methyl 2 , 6-dichlorobenzoate 1,1-dioxide (WIN 63,394), 3-amino-1,2,4-benzotriazine-1,4-dioxide (WIN 59,075), piperosulfam, piperosulphane, camptothecin, Acetominophen, acetylsalicylic acid, amiodarone, colestifmine, colestipol, cromolyn sodium, alb Roll, sucralfate, sulfasalazine, minoxidil, tempazepam, alprazolam, propoxyphene, auranofin, erythromycin, cyclosporine, acyclovir, ganciclobia, etoposide, mephalan, methotrexate, minoxantrone, daunorubicin, doxorubicin, megesterol, tamoxifen, tamoxifen Roxyprogesterone, nystatin, terbutaline, amphotericin B, aspirin, ibuprofen, naproxen, indomethacin, diclofenac, ketoprofen, flubiprofen, diflunisal, ethyl-3,5-diacetamide-2,4,6-triiodobenzoate (WINＷ8883) Ethyl (3,5-bis (acetylamino) -2,4,6-triiodobenzo Ilyloxy) acetate (WIN 12,901) and ethyl-2- (3,5-bis (acetylamino) -2,4,6-triiodobenzoyloxy) acetate (WIN 16,318) are representative examples. It is done.
　この発明の好ましい形態では、薬物がダナゾール（Ｄａｎａｚｏｌ）またはタクロリムス水和物のような免疫抑制剤、トラニラストのような抗アレルギー薬、プロゲステロンのようなステロイド、抗ウイルス薬、抗悪性腫瘍薬または抗炎症薬である。 In a preferred form of the invention, the drug is an immunosuppressant such as Danazol or tacrolimus hydrate, an antiallergic agent such as tranilast, a steroid such as progesterone, an antiviral agent, an antineoplastic agent or anti-inflammatory. It is a medicine.
　特に好ましい安定化剤・分散剤（界面活性剤）としては、ドデシルベンゼンスルホン酸ナトリウム、ドデシル硫酸ナトリウム、テトラデシル硫酸ナトリウム、ペンタデシル硫酸ナトリウム、オクチル硫酸ナトリウム、オレイン酸ナトリウム、ラウリル酸ナトリウム、ステアリン酸ナトリウム、ステアリン酸カルシウム、Ｔｗｅｅｎ２０およびＴｗｅｅｎ８０（これらは、ＩＣＩ Ｓｐｅｃｉａｌｔｙ Ｃｈｅｍｉｃａｌｓ から入手できる、ポリオキシエチレンソルビタン脂肪酸エステル類である）、ポリビニルピロリドン、チロキサポール、プルロニック（Ｐｌｕｒｏｎｉｃ）Ｆ６８およびＦ１０８（これらは、ＢＡＳＦから入手できるエチレンオキシドとプロピレンオキシドのブロックコポリマーである）、テトロニック（Ｔｅｔｒｏｎｉｃ）９０８（Ｔ９０８）（これは、ＢＡＳＦから入手できる、エチレンジアミンへのエチレンオキシドおよびプロピレンオキシドの連続付加物由来の４官能性ブロックコポリマーである）、デキストラン、レシチン、エーロゾル（Ａｅｒｏｓｏｌ）ＯＴ（これは、Ａｍｅｒｉｃａｎ Ｃｙａｎａｍｉｄ から入手できる、スルホコハク酸ナトリウムのジオクチルエステルである）、デュポノール（Ｄｕｐｏｎｏｌ）Ｐ（これは、ＤｕＰｏｎｔから入手できる、ラウリル硫酸ナトリウムである）、トリトン（Ｔｒｉｔｏｎ）Ｘ－２００（これは、Ｒｏｈｍ ａｎｄ Ｈａａｓ から入手できる、アルキルアリールポリエーテルスルホネートである）、カーボワックス（Ｃａｒｂｏｗａｘ）３３５０および９３４（これらは、Ｕｎｉｏｎ Ｃａｒｂｉｄｅ から入手できる、ポリエチレングリコール類である）、クロデスタ（Ｃｒｏｄｅｓｔａ）Ｆ－１１０（これは、Ｃｒｏｄａ Ｉｎｃ．から入手できる、シュークロースステアレートおよびシュークロースジステアレートの混合物である）、クロデスタ５Ｌ－４０（これはＣｒｏｄａ Ｉｎｃ．から入手できる）、ならびにＳＡ９０ＨＣＯ〔これは、Ｃ18Ｈ37ＣＨ2－（ＣＯＮ（ＣＨ3）ＣＨ2（ＣＨＯＨ）4ＣＨ2ＯＨ）2である〕、また、塩化ベンゼトニウム、塩化ベンザルコニウム等の４級アミン系界面活性剤やポリオキシエチレン高級アルコールエーテル類、グリセリン脂肪酸エステル類、ポリオキシエチレン硬化ヒマシ油、ポリオキシエチレン脂肪酸エステル、ポリオキシエチレンノニルフェニルエーテル、ポリオキシエチレンオクチルフェニルエーテル、ソルビタン脂肪酸エステル、プロピレングリコール脂肪酸エステル、脂肪酸ポリエチレングリコール、ポリグリセリン脂肪酸エステル、ショ糖脂肪酸エステル等の非イオン性界面活性剤類が挙げられる。目的の生体摂取物微粒子及び析出反応に応じて使い分ければよい。 Particularly preferred stabilizers / dispersants (surfactants) include sodium dodecylbenzenesulfonate, sodium dodecyl sulfate, sodium tetradecyl sulfate, sodium pentadecyl sulfate, sodium octyl sulfate, sodium oleate, sodium laurate, sodium stearate, Calcium stearate, Tween 20 and Tween 80 (these are polyoxyethylene sorbitan fatty acid esters available from ICI Specialty Chemicals), polyvinyl pyrrolidone, tyloxapol, Pluronic F68 and F108 (which are ethylene oxide available from BASF) A block copolymer of propylene oxide), Tetronic 908 (T908) (which is a tetrafunctional block copolymer derived from the continuous addition of ethylene oxide and propylene oxide to ethylenediamine, available from BASF), dextran, lecithin, Aerosol OT (which is the American Cyanamid) Is a dioctyl ester of sodium sulfosuccinate, Duponol P (which is sodium lauryl sulfate, available from DuPont), Triton X-200 (which is from Rohm and Haas Available are alkyl aryl polyether sulfonates), Carbowax 3350 and 934 (which are Union Carbide or Available polyethylene glycols), Crodesta F-110 (which is a mixture of sucrose stearate and sucrose distearate available from Croda Inc.), Clodesta 5L-40 (this Is available from Croda Inc.), as well as SA90HCO (which is C 18 H 37 CH 2 — (CON (CH 3 ) CH 2 (CHOH) 4 CH 2 OH) 2 ), benzethonium chloride, benzaza chloride Quaternary amine surfactants such as Luconium, polyoxyethylene higher alcohol ethers, glycerin fatty acid esters, polyoxyethylene hydrogenated castor oil, polyoxyethylene fatty acid esters, polyoxyethylene nonylphenyl ether, polyoxyethylene octyl Phenyl ether, sorbitan fatty acid esters, propylene glycol fatty acid esters, fatty acid polyethylene glycol, polyglycerin fatty acid esters, nonionic surfactants such as sucrose fatty acid esters. What is necessary is just to use properly according to the target living body intake fine particle and precipitation reaction.
　水溶性高分子としては、メチルセルロース、エチルセルロース、プロピルメチルセルロース、プロピルセルロース、カルボキシメチルセルロース、ポリビニルアルコール、ポリビニルピロリドン等を挙げることできる。
　本発明における該薬物の含有量は、特に制限はない。高濃度の懸濁液を作り、使用濃度に合わせて希釈して製剤とする事も可能である。 Examples of the water-soluble polymer include methyl cellulose, ethyl cellulose, propyl methyl cellulose, propyl cellulose, carboxymethyl cellulose, polyvinyl alcohol, and polyvinyl pyrrolidone.
The content of the drug in the present invention is not particularly limited. It is also possible to prepare a suspension with a high concentration and dilute it according to the concentration to be used.
　安定剤としては、エデト酸ナトリウム、亜硫酸ナトリウム、亜硫酸水素ナトリウム、チオ硫酸ナトリウム、ジブチルヒドロキシトルエン、トコフェロールなどを挙げることができる。 Examples of the stabilizer include sodium edetate, sodium sulfite, sodium hydrogen sulfite, sodium thiosulfate, dibutylhydroxytoluene, tocopherol and the like.
　保存剤としては、パラオキシ安息香酸エステル、クロロブタノール、フェニルエチルアルコール、塩化ベンザルコニウム、塩化ベンゼトニウム、グルコン酸クロルヘキシジン、アルキルポリアミノエチルグリシン類、ソルビン酸などが挙げることができる。 Examples of the preservative include paraoxybenzoic acid ester, chlorobutanol, phenylethyl alcohol, benzalkonium chloride, benzethonium chloride, chlorhexidine gluconate, alkylpolyaminoethylglycines, and sorbic acid.
　ｐＨ調整剤としては、塩酸、硫酸、酢酸、乳酸、クエン酸、酒石酸、リンゴ酸、リン酸、ホウ酸、水酸化ナトリウム、水酸化カリウム、水酸化カルシウム、モノエタノールアミン、ジエタノールアミン、ジエチルアミン、アンモニア及びこれらの塩類などを挙げることができる。 Examples of pH adjusters include hydrochloric acid, sulfuric acid, acetic acid, lactic acid, citric acid, tartaric acid, malic acid, phosphoric acid, boric acid, sodium hydroxide, potassium hydroxide, calcium hydroxide, monoethanolamine, diethanolamine, diethylamine, ammonia and These salts can be mentioned.
　等張化剤としては、塩化ナトリウム、塩化カリウム、塩化カルシウム、マンニトール等を挙げることができる。 Examples of isotonic agents include sodium chloride, potassium chloride, calcium chloride, mannitol and the like.
　本発明における前記生体摂取物微粒子原料を少なくとも１種類含む流体に用いる溶媒としては、超純水やイオン交換水などの水と、目的に応じてメチルアルコール、エチルアルコール、アセトン、ジメチルホルムアミド、ジメチルアセトアミド、ジメチルスルホキシドのような水混和性有機溶剤、オクタン、シクロヘキサン、ベンゼン、キシレン、ジエチルエーテル、酢酸エチルのような水不混和性有機溶剤を、目的に応じ適宜選んで実施できる。 As the solvent used in the fluid containing at least one kind of the raw material for living body intake in the present invention, water such as ultrapure water or ion exchange water, and methyl alcohol, ethyl alcohol, acetone, dimethylformamide, dimethylacetamide depending on the purpose. A water-miscible organic solvent such as dimethyl sulfoxide and a water-immiscible organic solvent such as octane, cyclohexane, benzene, xylene, diethyl ether, and ethyl acetate can be appropriately selected according to the purpose.
　なお、本発明の生体摂取物微粒子は、生体に摂取する事を目的とするものであれば特に限定されないが、例えば医薬品における薬物のように生体内に吸収し、生体内での効果を発現させる事を目的とするものや、造影剤としての硫酸バリウムのような、体内を通過させるものやドラッグデリバリーシステムにおける薬物成分の運搬用物質、または化粧料のように、生体皮膚に塗布するもの、及び食品と前記物質の中間体などが挙げられる。 The biologically ingestible particulate of the present invention is not particularly limited as long as it is intended to be ingested by the living body, but for example, it is absorbed into the living body like a drug in a pharmaceutical product and exhibits an in vivo effect. Those intended to be applied, those that pass through the body, such as barium sulfate as a contrast agent, those that are applied to living skin, such as substances for transporting drug components in drug delivery systems, or cosmetics, and Examples include foods and intermediates of the above substances.
　微粒子の析出反応は、図１に示す装置の、接近・離反可能に互いに対向して配設され、少なくとも一方が他方に対して回転する処理用面１，２間で強制的に均一混合しながら起こる。 The precipitation reaction of the fine particles is performed while forcibly and uniformly mixing between the processing surfaces 1 and 2 which are disposed so as to be able to approach and separate from each other in the apparatus shown in FIG. Occur.
　まず、一つの流路である第１導入部ｄ１より、前記の第１溶媒を含む溶液を、接近・離反可能に互いに対向して配設され、少なくとも一方が他方に対して回転する処理用面１，２間に導入して、この処理用面間に第１流体から構成された薄膜流体を作る。 First, from the first introduction part d1, which is one flow path, the solution containing the first solvent is disposed to face each other so as to be able to approach and leave, and at least one of the processing surfaces rotates with respect to the other. A thin film fluid composed of a first fluid is created between the processing surfaces.
　次いで別流路である第２導入部ｄ２より、第１溶媒よりも溶解度の低い第２溶媒となりうる溶媒を、前記第１流体から構成された薄膜流体に直接導入する。 Next, a solvent that can be a second solvent having a lower solubility than the first solvent is directly introduced into the thin film fluid composed of the first fluid from the second introduction part d2 that is a separate flow path.
　前記のように、流体の供給圧と回転する処理用面の間にかかる圧力との圧力バランスによって距離を固定された処理用面１，２間にて、第１溶媒を含む溶液と第２溶媒とが混合され、微粒子の析出反応を行う事が出来る。 As described above, the solution containing the first solvent and the second solvent are disposed between the processing surfaces 1 and 2 whose distance is fixed by the pressure balance between the fluid supply pressure and the pressure applied between the rotating processing surfaces. Can be mixed to perform precipitation reaction of fine particles.
　なお、処理用面１，２間にて前記反応を行う事が出来れば良いので、前記とは逆に、第１導入部ｄ１より第２溶媒を導入し、第２導入部ｄ２より第１溶媒を含む溶液を導入するものであっても良い。つまり、各溶媒における第１、第２という表現は、複数存在する溶媒の第ｎ番目であるという、識別のための意味合いを持つに過ぎないものであり、第３以上の溶媒も存在し得る。 Note that, as long as the reaction can be performed between the processing surfaces 1 and 2, the second solvent is introduced from the first introduction part d 1 and the first solvent is introduced from the second introduction part d 2. It is also possible to introduce a solution containing. In other words, the expressions “first” and “second” in each solvent only have a meaning for identification that they are the n-th of a plurality of solvents, and third or more solvents may exist.
　前述のように、第１導入部ｄ１、第２導入部ｄ２以外に第３導入部ｄ３を処理装置に設けることもできるが、この場合にあっては、例えば各導入部から、第１溶媒を含む溶液、第２溶媒、安定化剤・分散剤を含む溶液をそれぞれ別々に処理装置に導入することが可能である。そうすると、各溶液の濃度や圧力を個々に管理することができ、析出反応をより精密に制御することができる。第４以上の導入部を設けた場合も同様であって、このように処理装置へ導入する流体を細分化できる。 As described above, in addition to the first introduction part d1 and the second introduction part d2, a third introduction part d3 can be provided in the processing apparatus. In this case, for example, the first solvent is introduced from each introduction part. The solution containing the solution, the second solvent, and the solution containing the stabilizer / dispersant can be separately introduced into the processing apparatus. If it does so, the density | concentration and pressure of each solution can be managed separately, and precipitation reaction can be controlled more precisely. The same applies to the case where the fourth or more introduction portions are provided, and the fluid to be introduced into the processing apparatus can be subdivided in this way.
　以下本発明について実施例を掲げて更に詳しく説明するが、本発明はこれらの実施例のみに限定されるものではない。 Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to these examples.
　なお、以下の実施例において、「中央から」というのは、図１に示す処理装置の「第１導入部ｄ１から」という意味であり、第１流体は、第１導入部ｄ１から導入される、前述の第１被処理流動体を指し、第２流体は、図１に示す処理装置の第２導入部ｄ２から導入される、前述の第２被処理流動体を指す。また、第２導入部ｄ２の開口部ｄ２０として、図２（Ｂ）に点線で示すように、処理用面２の中央の開口を取り巻く同心円状の円環形状のものを用いた。 In the following embodiments, “from the center” means “from the first introduction part d1” of the processing apparatus shown in FIG. 1, and the first fluid is introduced from the first introduction part d1. The first fluid to be treated refers to the second fluid to be treated, which is introduced from the second introduction part d2 of the treatment apparatus shown in FIG. Further, as the opening d20 of the second introduction part d2, a concentric annular shape surrounding the central opening of the processing surface 2 was used as shown by a dotted line in FIG.
　ＴＥＭ観察には、日本電子（株）製、ＪＥＭ－２１００を用いて、複数視野について一次粒子径を観察した。ＴＥＭ観察の観測条件としては、実施例１～４０については、観察倍率を５万倍以上とし、ＴＥＭ観察にて確認された微粒子１００個の一次粒子径の平均値を平均粒子径として採用し、実施例４１～４９については、観察倍率を３万倍以上とし、ＴＥＭ観察にて確認された微粒子１００個の一次粒子径の平均値を平均粒子径として採用した。 In the TEM observation, the primary particle diameter was observed for a plurality of visual fields using JEM-2100 manufactured by JEOL. As the observation conditions for TEM observation, for Examples 1 to 40, the observation magnification was 50,000 times or more, and the average value of the primary particle diameters of 100 fine particles confirmed by TEM observation was adopted as the average particle diameter. For Examples 41 to 49, the observation magnification was 30,000 times or more, and the average value of the primary particle diameters of 100 fine particles confirmed by TEM observation was adopted as the average particle diameter.
　Ｘ線回折（ＸＲＤ）測定には、粉末Ｘ線回折測定装置　Ｘ‘Ｐｅｒｔ ＰＲＯ ＭＰＤ（ＸＲＤ　スペクトリス ＰＡＮａｌｙｔｉｃａｌ事業部製）を使用した。
　実施例１～４０については、測定条件は，Ｃｕ対陰極，管電圧４５ｋＶ，管電流４０ｍＡ，０．０１６ｓｔｅｐ／１０ｓｅｃ、測定範囲は１０～６０［°２Ｔｈｅｔａ］（Ｃｕ）である。得られた微粒子の結晶化度と特定結晶型の構成比率をＸＲＤ測定結果より算出した。結晶化度は、各実験において得られたXRD測定結果より、顔料原末の結晶化度を１００％として、コンスタントバックグラウンド法にて算出した。β型結晶である特定結晶型の構成比率（以下、β型結晶比率）は、測定結果より、β型結晶に特徴的なピークとして現れる２７．５°付近のピークの強度Ｉβと、α型結晶に特徴的なピークとして現れる２６．５°付近のピークの強度Ｉαとを用いて、以下の式（４）にて算出した。
β型結晶比率＝（Ｉβ／（Ｉα＋Ｉβ））×１００［％］・・・式（４）
　また、実施例４１～４９については、測定条件は，Ｃｕ対陰極，管電圧４５ｋＶ，管電流４０ｍＡ，０．０１６ｓｔｅｐ／１０ｓｅｃ、測定範囲は１０～４５［°２Ｔｈｅｔａ］（Ｃｕ）である。得られた微粒子の結晶化度と特定結晶型の構成比率をＸＲＤ測定結果より算出した。結晶化度は、各実験において得られたＸＲＤ測定結果より、原末の結晶化度を１００％として、コンスタントバックグラウンド法にて算出した。γ型結晶である特定結晶型の構成比率（以下、γ型結晶比率）は、測定結果より、γ型結晶に特徴的なピークとして現れる、２９．５°付近のピークの強度Ｉγと、α型結晶に特徴的なピークとして現れる、１５．５°付近のピークの強度Ｉαと、β型結晶に特徴的なピークとして現れる１０．５°付近のピークの強度Ｉβとを用いて、以下の式（５）にて算出した。
γ型結晶比率＝（Ｉγ／（Ｉγ＋Ｉα＋Ｉβ））×１００［％］・・・式（５）　　　 For the X-ray diffraction (XRD) measurement, a powder X-ray diffraction measurement apparatus X'Pert PRO MPD (manufactured by XRD Spectris PANalytical Division) was used.
For Examples 1 to 40, the measurement conditions are Cu counter cathode, tube voltage 45 kV, tube current 40 mA, 0.016 step / 10 sec, and the measurement range is 10 to 60 [° 2 Theta] (Cu). The degree of crystallinity of the obtained fine particles and the composition ratio of the specific crystal type were calculated from the XRD measurement results. The crystallinity was calculated by the constant background method from the XRD measurement results obtained in each experiment, assuming that the crystallinity of the pigment bulk powder was 100%. The composition ratio of the specific crystal type that is a β-type crystal (hereinafter referred to as β-type crystal ratio) is determined from the measurement results, the peak intensity Iβ near 27.5 ° that appears as a characteristic peak in the β-type crystal, and the α-type crystal. Using the intensity Iα of the peak near 26.5 ° that appears as a characteristic peak in FIG.
β-type crystal ratio = (Iβ / (Iα + Iβ)) × 100 [%] (4)
For Examples 41 to 49, the measurement conditions are Cu counter cathode, tube voltage 45 kV, tube current 40 mA, 0.016 step / 10 sec, and the measurement range is 10 to 45 [° 2 Theta] (Cu). The degree of crystallinity of the obtained fine particles and the composition ratio of the specific crystal type were calculated from the XRD measurement results. The crystallinity was calculated by the constant background method from the XRD measurement results obtained in each experiment, assuming that the crystallinity of the bulk powder was 100%. The composition ratio of the specific crystal type that is the γ-type crystal (hereinafter referred to as the γ-type crystal ratio) is determined from the measurement result, the peak intensity Iγ near 29.5 ° that appears as a characteristic peak in the γ-type crystal, and the α-type crystal. Using the intensity Iα of the peak near 15.5 ° appearing as a characteristic peak in the crystal and the intensity Iβ of the peak near 10.5 ° appearing as a characteristic peak in the β-type crystal, the following formula ( Calculated in 5).
γ-type crystal ratio = (Iγ / (Iγ + Iα + Iβ)) × 100 [%] (5)
（アシッドペースティング法を用いたＰＲ１２２微粒子の作製）（実施例１～３）
　図１に示される流体処理装置を用いて、微粒子原料溶液である顔料溶液と析出溶媒とを、対向して配設された、接近・離反可能な処理用面をもつ、少なくとも一方が他方に対して回転する処理用面１，２間に形成される薄膜流体中で混合し、薄膜流体中で顔料微粒子を析出させた。顔料溶液の調製には、回転する攪拌翼を有する攪拌機を用いて行い、攪拌エネルギーを規定する３つの条件（攪拌時間、攪拌翼の周速度、微粒子原料溶液の温度）のうち少なくとも１つを変化させることにより、攪拌エネルギーを増減させた。実施例１～３においては、顔料溶液の温度（調製温度）を変化させることにより、攪拌エネルギーを増減させた。 (Preparation of PR122 fine particles using acid pasting method) (Examples 1 to 3)
Using the fluid processing apparatus shown in FIG. 1, at least one of the pigment solution, which is a fine particle raw material solution, and a deposition solvent are disposed opposite to each other and have a processing surface that can be approached and separated, with respect to the other. Then, the mixture was mixed in a thin film fluid formed between the processing surfaces 1 and 2 rotating, and pigment fine particles were precipitated in the thin film fluid. The pigment solution is prepared using a stirrer having a rotating stirring blade, and at least one of the three conditions (stirring time, stirring blade peripheral speed, and temperature of the fine particle raw material solution) defining the stirring energy is changed. The stirring energy was increased or decreased. In Examples 1 to 3, the stirring energy was increased or decreased by changing the temperature (preparation temperature) of the pigment solution.
　まず、図４及び図５に示す、回転する攪拌翼を有する攪拌機（クレアミックス（エム・テクニック株式会社製））を用いて、顔料溶液を調製した。具体的には、クレアミックスを用いて、１０ｗｔ％発煙硫酸にＰＲ１２２を全体量として３ｗｔ％になるように投入し、窒素雰囲気において表２の調製時間、調製温度、攪拌翼の周速度にて顔料溶液を攪拌し、３ｗｔ％ＰＲ１２２を１０ｗｔ％発煙硫酸に溶解させた。 First, a pigment solution was prepared using a stirrer (CLEAMIX (manufactured by M Technique Co., Ltd.)) having rotating stirring blades as shown in FIGS. Specifically, using CLEARMIX, PR122 was added to 10 wt% fuming sulfuric acid so that the total amount would be 3 wt%, and the pigment was prepared in the nitrogen atmosphere at the preparation time, preparation temperature, and peripheral speed of the stirring blade in Table 2. The solution was stirred and 3 wt% PR122 was dissolved in 10 wt% fuming sulfuric acid.
　次に、中央から第１流体の析出溶媒として、メタノール（ＭｅＯＨ）を、供給圧力／背圧力＝０．１２１ＭＰａＧ／０．０２０ＭＰａＧ、回転数２５００ｒｐｍで送液しながら、顔料溶液を第２流体として処理用面間に導入し、第１流体と第２流体とを薄膜流体中で混合した。ＰＲ１２２微粒子分散液が処理用面１，２間より吐出された。吐出されたＰＲ１２２微粒子分散液中より不純物を除去するために、ＰＲ１２２微粒子分散液を緩く凝集させ、洗浄操作として遠心分離機（×１８０００Ｇ）にてＰＲ１２２微粒子分散液を沈降させ、上澄み液を除去した後、純水を加えてＰＲ１２２微粒子分散液を再分散し、再度遠心分離機を用いて沈降させた。前記洗浄操作を３回行ったあと、最終的に得られたＰＲ１２２微粒子分散液のペーストを２５℃、－０．１ＭＰａＧにて真空乾燥し、ＰＲ１２２微粒子の乾燥粉体を得た。得られたＰＲ１２２微粒子の乾燥粉体についてＴＥＭ観察とＸＲＤ測定を行い、平均粒子径、結晶化度並びにβ型結晶比率を求めた。また、結晶化度並びにβ型結晶比率のそれぞれの値については、平均粒子径に対する比率（以下、ＰＲ１２２微粒子の結晶化度／平均粒子径並びにＰＲ１２２微粒子のβ型結晶比率／平均粒子径）を評価した。これは、ＸＲＤ測定するＰＲ１２２微粒子の粒子径の違いにより、ＸＲＤ測定における散乱強度に差異がでるため、粒子径で除算することで規格化を行うためである。なお、本発明において前記のように平均粒子径で除算して数値変化をみる場合、粒子径の変化の幅がナノオーダーで３桁の範囲内にある場合に好適であり、２桁の範囲内に止まる場合がより好適である。
　表１に、第１流体と第２流体の処理条件（処方及び運転条件）を示す。表２に、第２流体の調製条件と得られた結果を示す。また、表１に示す第１流体及び第２流体の目標温度は、第１流体と第２流体のそれぞれを処理装置に導入する際の温調器（加熱・冷却）の設定温度である。 Next, the pigment solution is treated as the second fluid while feeding methanol (MeOH) from the center as methanol (MeOH) at a supply pressure / back pressure of 0.121 MPaG / 0.020 MPaG and a rotational speed of 2500 rpm. The first fluid and the second fluid were mixed in the thin film fluid by introducing between the working surfaces. PR122 fine particle dispersion was discharged from between the processing surfaces 1 and 2. In order to remove impurities from the discharged PR122 fine particle dispersion, the PR122 fine particle dispersion was loosely agglomerated, and as a washing operation, the PR122 fine particle dispersion was precipitated by a centrifuge (× 18000G), and the supernatant was removed. Thereafter, pure water was added to re-disperse the PR122 fine particle dispersion, and the precipitate was precipitated again using a centrifuge. After performing the washing operation three times, the finally obtained paste of the PR122 fine particle dispersion was vacuum dried at 25 ° C. and −0.1 MPaG to obtain a dry powder of PR122 fine particles. The obtained dry powder of PR122 fine particles was subjected to TEM observation and XRD measurement, and the average particle diameter, crystallinity, and β-type crystal ratio were determined. Further, for each value of the crystallinity and β-type crystal ratio, the ratio to the average particle size (hereinafter, the crystallinity of PR122 fine particles / average particle size and the β-type crystal ratio of PR122 fine particles / average particle size) was evaluated. did. This is because the scattering intensity in the XRD measurement varies depending on the particle diameter of the PR122 fine particles to be measured by XRD, and normalization is performed by dividing by the particle diameter. In the present invention, when the numerical change is observed by dividing by the average particle diameter as described above, it is suitable when the width of the change in the particle diameter is in the nano-order range of 3 digits, and within the 2-digit range. It is more preferable to stop at
Table 1 shows the processing conditions (prescription and operating conditions) of the first fluid and the second fluid. Table 2 shows the conditions for preparing the second fluid and the results obtained. The target temperatures of the first fluid and the second fluid shown in Table 1 are set temperatures of the temperature controller (heating / cooling) when each of the first fluid and the second fluid is introduced into the processing apparatus.
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000001
Figure JPOXMLDOC01-appb-T000002
Figure JPOXMLDOC01-appb-T000002
　図６に、実施例１～３にて、第２流体の調製温度に対するＰＲ１２２微粒子の結晶化度／平均粒子径及びβ型結晶比率／平均粒子径の変化を示す。図６より、第２流体の調製温度が上昇すると、得られたＰＲ１２２微粒子の結晶化度／平均粒子径、β型結晶比率／平均粒子径の数値がとも上昇する傾向が認められる。
　また、表２より、第２流体の調製温度が上昇すると、得られたＰＲ１２２微粒子の平均粒子径が小さくなることが認められる。 FIG. 6 shows changes in crystallinity / average particle diameter and β-type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation temperature of the second fluid in Examples 1 to 3. From FIG. 6, it can be seen that when the preparation temperature of the second fluid increases, the numerical values of the degree of crystallinity / average particle diameter and β-type crystal ratio / average particle diameter of the obtained PR122 fine particles increase.
Further, from Table 2, it is recognized that the average particle diameter of the obtained PR122 fine particles decreases as the preparation temperature of the second fluid increases.
（実施例４～１６）
　顔料溶液の調製条件を表３～５の何れかとした以外は、実施例１～３の場合と同様に実施して、ＰＲ１２２微粒子の乾燥粉体を得た。結果を表３～５に示す。実施例４～１６においては、第２流体である顔料溶液の攪拌時間（調製時間）を変化させることにより、攪拌エネルギーを増減させた。 (Examples 4 to 16)
A dry powder of PR122 fine particles was obtained in the same manner as in Examples 1 to 3 except that the preparation conditions of the pigment solution were changed to any of Tables 3 to 5. The results are shown in Tables 3-5. In Examples 4 to 16, the stirring energy was increased or decreased by changing the stirring time (preparation time) of the pigment solution as the second fluid.
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000003
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000004
Figure JPOXMLDOC01-appb-T000005
Figure JPOXMLDOC01-appb-T000005
　実施例４～７にて、第２流体の調製時間に対するＰＲ１２２微粒子の結晶化度／平均粒子径及びβ型結晶比率／平均粒子径の変化を図７に、実施例８～１１にて、第２流体の調製時間に対するＰＲ１２２微粒子の結晶化度／平均粒子径及びβ型結晶比率／平均粒子径の変化を図８に、実施例１２～１６にて、第２流体の調製時間に対するＰＲ１２２微粒子の結晶化度／平均粒子径及びβ型結晶比率／平均粒子径の変化を図９に示す。また、実施例８～１１、実施例１２、１３、１５、１６にて、第２流体の調製時間に対するＰＲ１２２微粒子の結晶化度／平均粒子径の変化を図１０に、実施例８～１１、実施例１２、１３、１５、１６にて、第２流体の調製時間に対するＰＲ１２２微粒子のβ型結晶比率／平均粒子径の変化を図１１に示す。
　図７～９より、第２流体の調製時間が増大すると、得られたＰＲ１２２微粒子の結晶化度／平均粒子径、β型結晶比率／平均粒子径の数値がともに増加していることが認められる。また、表３～５より、第２流体の調製時間が増大すると、得られたＰＲ１２２微粒子の平均粒子径が小さくなることが認められる。
　また、図１０～１１より、第２流体の調製時間に加え第２流体である顔料溶液調製時の攪拌翼の周速度を変化させた実施例においても、第２流体の調製時間が増大すると、得られたＰＲ１２２微粒子の結晶化度／平均粒子径、β型結晶比率／平均粒子径の数値がともに増加していることが認められる。 In Examples 4 to 7, changes in the degree of crystallinity / average particle diameter and β-type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid are shown in FIG. Changes in crystallinity / average particle diameter and β-type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation time of two fluids are shown in FIG. Changes in crystallinity / average particle size and β-type crystal ratio / average particle size are shown in FIG. In Examples 8 to 11 and Examples 12, 13, 15, and 16, the change in crystallinity / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid is shown in FIG. FIG. 11 shows changes in β-type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid in Examples 12, 13, 15, and 16.
7 to 9, it can be seen that as the preparation time of the second fluid increases, the numerical values of crystallinity / average particle diameter and β-type crystal ratio / average particle diameter of the obtained PR122 fine particles both increase. . Further, from Tables 3 to 5, it is recognized that the average particle diameter of the obtained PR122 fine particles decreases as the preparation time of the second fluid increases.
In addition, from FIGS. 10 to 11, in the example in which the peripheral speed of the stirring blade at the time of preparing the pigment solution as the second fluid was changed in addition to the preparation time of the second fluid, when the preparation time of the second fluid increased, It can be seen that the crystallinity / average particle diameter and β-type crystal ratio / average particle diameter of the obtained PR122 fine particles are both increased.
（実施例１７～２２）
　顔料溶液の調製条件を表６又は７とした以外は、実施例１～３の場合と同様に実施して、ＰＲ１２２微粒子の乾燥粉体を得た。結果を表６～７に示す。実施例１７～２２においては、第２流体である顔料溶液調製時の攪拌翼の周速度を変化させることにより、攪拌エネルギーを増減させた。 (Examples 17 to 22)
A dry powder of PR122 fine particles was obtained in the same manner as in Examples 1 to 3 except that the preparation conditions of the pigment solution were changed to Table 6 or 7. The results are shown in Tables 6-7. In Examples 17 to 22, the stirring energy was increased or decreased by changing the peripheral speed of the stirring blade when preparing the pigment solution as the second fluid.
Figure JPOXMLDOC01-appb-T000006
Figure JPOXMLDOC01-appb-T000006
Figure JPOXMLDOC01-appb-T000007
Figure JPOXMLDOC01-appb-T000007
　実施例１７～２２にて、第２流体調製時の攪拌翼の周速度に対するＰＲ１２２微粒子の結晶化度／平均粒子径の変化を図１２に、実施例１７～２２にて、第２流体調製時の攪拌翼の周速度に対するＰＲ１２２微粒子のβ型結晶比率／平均粒子径の変化を図１３に示す。
　図１２～１３より、第２流体調製時の攪拌翼の周速度が増大すると、得られたＰＲ１２２微粒子の結晶化度／平均粒子径、β型結晶比率／平均粒子径の数値がとも上昇する傾向が認められ、前記の周速度の変化に加え第２流体の調製時間を変化させた実施例においても、同様の傾向が認められた。
　また、表６～７より、第２流体調製時の攪拌翼の周速度が増大すると、得られたＰＲ１２２微粒子の平均粒子径が小さくなることが認められる。 In Examples 17 to 22, the change in crystallinity / average particle diameter of PR122 fine particles with respect to the peripheral speed of the stirring blade at the time of preparing the second fluid is shown in FIG. 12, and in Examples 17 to 22 at the time of preparing the second fluid FIG. 13 shows changes in the β-type crystal ratio / average particle diameter of PR122 fine particles with respect to the peripheral speed of the stirring blade.
12 to 13, when the peripheral speed of the stirring blade at the time of preparing the second fluid increases, the numerical values of crystallinity / average particle diameter, β-type crystal ratio / average particle diameter of the obtained PR122 fine particles tend to increase. The same tendency was recognized also in the Example which changed the preparation time of the 2nd fluid in addition to the change of the said peripheral velocity.
Further, from Tables 6 to 7, it is recognized that the average particle diameter of the obtained PR122 fine particles decreases as the peripheral speed of the stirring blade during the second fluid preparation increases.
　本発明は、前記の実施例の結果から、攪拌エネルギーを増減させるべく、第２流体の調製条件の優先度の設定に関して、次のような事項を導くことができる。
　実施例１～３の結果より、第２流体の調製温度を６０℃に保持して実施した場合（実施例３）、調製に費やす撹拌時間が３０分と短時間で、かつ攪拌機の攪拌翼の周速度が１８．８５ｍ／ｓｅｃの比較的低速である。しかしながら、この場合より更に長い撹拌時間を費やし、前記の周速度を更に高速に保持した調製時の温度が比較的低温での他の場合（実施例１３～１６）と比較すると、実施例３においては、得られたＰＲ１２２に関して平均粒子径の小さい微粒子を得ることができ、調製温度の高低が微粒子の性状／特性に及ぼす影響が最も強い。攪拌時間を１８０分と充分に長く費やした実施例１６において、ようやく実施例３の結果と同等となり、得られたＰＲ１２２に関して平均粒子径の小さい微粒子を得ることができた。また、実施例３と実施例２１，２２の対比からも、第２流体の調製温度が比較的低温の場合は、前記の周速度を更に高速に保持し、更に長い撹拌時間を費やしても、得られたＰＲ１２２微粒子の平均粒子径が実施例３ほど小さくならない。つまり、実施例３のように、第２流体の調製温度さえ少し高めに維持すれば、撹拌時間を短くし、前記の周速度を低く抑えても、平均粒子径が小さい微粒子を得られることになる。
　実施例４～１６の結果より、第２流体の調製温度を比較的低温に保持し、攪拌機の攪拌翼の周速度を比較的低速にしても充分に長い攪拌時間を確保すれば（例えば、実施例７や実施例１１）、実施例３の結果と同等となり、得られたＰＲ１２２に関して平均粒子径の小さい微粒子を得ることができることから、調製温度に次いで撹拌時間の長短が微粒子の性状／特性に対して及ぼす影響が強い。つまり、実施例７や実施例１１のように、第２流体の調製温度が比較的低温で、かつ前記の周速度が比較的低速であっても、充分に長い撹拌時間さえ確保すれば、実施例３で得られたＰＲ１２２微粒子の平均粒子径と同等の、平均粒子径が小さい微粒子を得ることができる。また実施例１７～２２のように、比較的短い撹拌時間同士で比較しても、攪拌機の攪拌翼の周速度が同一ならば、撹拌時間の長い方が、得られたＰＲ１２２に関して平均粒子径の小さい微粒子を得ることができることからも、撹拌時間の長短が微粒子の性状／特性に及ぼす影響は明らかである。
　実施例１７～２２の結果より、攪拌機の攪拌翼の周速度の高低変化は、得られたＰＲ１２２微粒子の平均粒子径に及ぼす影響があまり強くない。同一の撹拌時間同士の実施例１７と実施例１８、実施例２０と実施例２１で比べると、前記の周速度が１８．８５ｍ／ｓｅｃと２５．１３ｍ／ｓｅｃでは、得られたＰＲ１２２微粒子の平均粒子径において大きな差が現れない。前記の周速度が３１．４２ｍ／ｓｅｃである実施例１９と実施例２２では、前記の周速度が１８．８５ｍ／ｓｅｃと２５．１３ｍ／ｓｅｃである上述の実施例に対して、得られたＰＲ１２２微粒子の平均粒子径において差が現れるが、得られたＰＲ１２２微粒子の平均粒子径が実施例１～３、実施例４～１６の結果に及んでいない。
　また、前記の記載と結晶化度、β型結晶比率との関係性についても同じ対応関係になる。なぜならば、結晶化度、β型結晶比率を平均粒子径で除算してないときは、明確な数値的変化が現れ難かったが、結晶化度／平均粒子径、β型結晶比率／平均粒子径でみて初めて明確な数値的変化がわかるようになった。結晶化度、β型結晶比率の変化量が小さくても、平均粒子径の変化量が大きいので、除算すると結果的に差が発生してくる。結晶化度／平均粒子径、β型結晶比率／平均粒子径の数値が大きいほど好ましいと判断している。微粒子のように粒子が小さくなると、ＸＲＤの測定結果として、ピークがブロードになり易く、結晶化度、β型結晶比率が低くなり易い。故に、結晶化度やβ型結晶比率を評価する際には、粒子径との関係を踏まえて行う必要がある。
　なお、目的とされる微粒子の粒子径や、色目や着色力、耐久性を評価する指標となる「結晶化度」、「β型結晶比率」は、微粒子の用途に応じて当然異なることから、微粒子の用途に応じた制御を行えばよい。
　また、本発明において前記のように平均粒子径で除算して数値変化をみる場合、粒子径の変化の幅がナノオーダーで３桁の範囲内にある場合に好適であり、２桁の範囲内に止まる場合がより好適である。 The present invention can derive the following matters regarding the setting of the priority of the preparation conditions of the second fluid in order to increase or decrease the stirring energy from the results of the above-described embodiment.
From the results of Examples 1 to 3, when the second fluid was prepared with the preparation temperature maintained at 60 ° C. (Example 3), the stirring time spent for preparation was as short as 30 minutes, and the stirring blade of the stirrer The peripheral speed is a relatively low speed of 18.85 m / sec. However, in comparison with the other cases (Examples 13 to 16) in which the temperature during preparation in which a longer stirring time was consumed and the peripheral speed was maintained at a higher speed than in this case was relatively low (Examples 13 to 16), Can obtain fine particles having a small average particle diameter with respect to the obtained PR122, and the influence of the preparation temperature on the properties / characteristics of the fine particles is the strongest. In Example 16 where the stirring time was sufficiently long as 180 minutes, it finally became the same as the result of Example 3, and it was possible to obtain fine particles having a small average particle diameter with respect to the obtained PR122. Also, from the comparison between Example 3 and Examples 21 and 22, when the preparation temperature of the second fluid is relatively low, even if the peripheral speed is kept higher and a longer stirring time is spent, The average particle diameter of the obtained PR122 fine particles is not as small as Example 3. That is, as in Example 3, if the preparation temperature of the second fluid is kept slightly higher, fine particles having a small average particle diameter can be obtained even if the stirring time is shortened and the peripheral speed is kept low. Become.
From the results of Examples 4 to 16, if the preparation temperature of the second fluid is kept at a relatively low temperature and the peripheral speed of the stirring blade of the stirrer is made relatively low, a sufficiently long stirring time can be secured (for example, implementation) The results are the same as those of Example 7 and Example 11) and Example 3, and it is possible to obtain fine particles having a small average particle diameter with respect to the obtained PR122. The effect on it is strong. That is, as in Example 7 and Example 11, even if the preparation temperature of the second fluid is relatively low and the peripheral speed is relatively low, as long as a sufficiently long stirring time is ensured, Fine particles having a small average particle diameter equivalent to the average particle diameter of the PR122 fine particles obtained in Example 3 can be obtained. In addition, as in Examples 17 to 22, even when the stirring times are relatively short, if the peripheral speed of the stirring blades of the stirrer is the same, the longer the stirring time, the larger the average particle size of the obtained PR122. From the fact that small fine particles can be obtained, the influence of the length of the stirring time on the properties / characteristics of the fine particles is clear.
From the results of Examples 17 to 22, the change in the peripheral speed of the stirring blade of the stirrer has little influence on the average particle diameter of the obtained PR122 fine particles. Comparing Example 17 and Example 18 and Example 20 and Example 21 with the same stirring time, the average of the obtained PR122 fine particles was obtained when the peripheral speed was 18.85 m / sec and 25.13 m / sec. There is no significant difference in particle size. Example 19 and Example 22 in which the peripheral speed was 31.42 m / sec were obtained in comparison with the above-described examples in which the peripheral speed was 18.85 m / sec and 25.13 m / sec. Although a difference appears in the average particle size of the PR122 fine particles, the average particle size of the obtained PR122 fine particles does not reach the results of Examples 1 to 3 and Examples 4 to 16.
In addition, the same relationship is also obtained for the relationship between the above description, the degree of crystallinity, and the β-type crystal ratio. This is because, when the crystallinity and β-type crystal ratio are not divided by the average particle size, it was difficult to show a clear numerical change, but crystallinity / average particle size, β-type crystal ratio / average particle size. For the first time, a clear numerical change became apparent. Even if the amount of change in crystallinity and β-type crystal ratio is small, the amount of change in the average particle size is large, so that a difference occurs as a result when dividing. It is judged that the larger the numerical values of crystallinity / average particle diameter and β-type crystal ratio / average particle diameter, the better. When the particle is small like a fine particle, the peak of the XRD measurement is likely to be broad, and the crystallinity and β-type crystal ratio are likely to be low. Therefore, when evaluating the degree of crystallinity and the β-type crystal ratio, it is necessary to take into account the relationship with the particle size.
Note that the particle size of fine particles, the color and coloring power, and the “crystallinity”, which is an index for evaluating durability, and the “β-type crystal ratio” naturally differ depending on the use of the fine particles. What is necessary is just to perform control according to the use of fine particles.
Further, in the present invention, when the numerical change is observed by dividing by the average particle diameter as described above, it is suitable when the width of the change in the particle diameter is in the range of 3 digits in the nano order, and in the range of 2 digits. It is more preferable to stop at
（アルカリペースト法を用いたＰＲ１２２微粒子の作製）（実施例２３～４０）
　図１に示される流体処理装置を用いて、微粒子原料溶液である顔料溶液と析出溶媒とを、対向して配設された、接近・離反可能な処理用面をもつ、少なくとも一方が他方に対して回転する処理用面１，２間に形成される薄膜流体中で混合し、薄膜流体中で顔料微粒子を析出させた。顔料溶液の調製には、回転する攪拌翼を有する攪拌機を用いて行い、攪拌エネルギーを規定する３つの条件（攪拌時間、攪拌翼の周速度、微粒子原料溶液の温度）のうち顔料溶液の温度（調製温度）及び／又は攪拌時間（調製時間）を変化させることにより、攪拌エネルギーを増減させた。 (Preparation of PR122 fine particles using alkali paste method) (Examples 23 to 40)
Using the fluid processing apparatus shown in FIG. 1, at least one of the pigment solution, which is a fine particle raw material solution, and a deposition solvent are disposed opposite to each other and have a processing surface that can be approached and separated, with respect to the other. Then, the mixture was mixed in a thin film fluid formed between the processing surfaces 1 and 2 rotating, and pigment fine particles were precipitated in the thin film fluid. The pigment solution is prepared using a stirrer having a rotating stirring blade, and the temperature of the pigment solution (the stirring time, the peripheral speed of the stirring blade, and the temperature of the fine particle raw material solution) among the three conditions that define the stirring energy ( The stirring energy was increased or decreased by changing the preparation temperature) and / or the stirring time (preparation time).
　まず、図４及び図５に示す、回転する攪拌翼を有する攪拌機（クレアミックス（エム・テクニック株式会社製））を用いて、顔料溶液を調製した。具体的には、クレアミックスを用いて、重量比でジメチルスルホキシド／純水（ＰＷ）／水酸化カリウム（ＫＯＨ）＝７３．５／２３．１７／１．３７にて混合した混合溶媒を表９又は表１０の攪拌翼の周速度で攪拌しながらＰＲ１２２を投入し、重量比でジメチルスルホキシド／純水（ＰＷ）／水酸化カリウム（ＫＯＨ）／ＰＲ１２２＝７３．５／２３．１７／１．３７／１．９６となるように（１．９６ｗｔ％ＰＲ１２２溶液）、表９又は表１０の調製時間、調製温度にて顔料溶液を攪拌し、１．９６ｗｔ％ＰＲ１２２溶液を調製した。 First, a pigment solution was prepared using a stirrer (CLEAMIX (manufactured by M Technique Co., Ltd.)) having rotating stirring blades as shown in FIGS. More specifically, Table 9 shows a mixed solvent in which Clairemix was used and mixed at a weight ratio of dimethyl sulfoxide / pure water (PW) / potassium hydroxide (KOH) = 73.5 / 23.17 / 1.37. Alternatively, PR122 is added while stirring at the peripheral speed of the stirring blade of Table 10, and dimethyl sulfoxide / pure water (PW) / potassium hydroxide (KOH) /PR122=73.5/23.17/1.37 in weight ratio. /1.96 (1.96 wt% PR122 solution), the pigment solution was stirred at the preparation time and preparation temperature shown in Table 9 or Table 10 to prepare a 1.96 wt% PR122 solution.
　次に、中央から第１流体の析出溶媒として、２０ｗｔ％酢酸／メタノール（ＭｅＯＨ）を、供給圧力／背圧力＝０．１２１ＭＰａＧ／０．０２０ＭＰａＧ、回転数２５００ｒｐｍで送液しながら、顔料溶液を第２流体として処理用面間に導入し、第１流体と第２流体とを薄膜流体中で混合した。ＰＲ１２２微粒子分散液が処理用面１，２間より吐出された。吐出されたＰＲ１２２微粒子分散液中より不純物を除去するために、ＰＲ１２２微粒子分散液を緩く凝集させ、洗浄操作として遠心分離機（×１８０００Ｇ）にてＰＲ１２２微粒子分散液を沈降させ、上澄み液を除去した後、純水を加えてＰＲ１２２微粒子分散液を再分散し、再度遠心分離機を用いて沈降させた。前記洗浄操作を３回行ったあと、最終的に得られたＰＲ１２２微粒子分散液のペーストを５０℃、－０．１ＭＰａＧにて真空乾燥し、ＰＲ１２２微粒子の乾燥粉体を得た。得られたＰＲ１２２微粒子の乾燥粉体についてＴＥＭ観察とＸＲＤ測定を行い、粒子径、結晶化度並びにβ型結晶比率を求めた。また、結晶化度並びにβ型結晶比率のそれぞれの値については、実施例１～２２と同様、平均粒子径に対する割合（以下、ＰＲ１２２微粒子の結晶化度／平均粒子径並びにＰＲ１２２微粒子のβ型結晶比率／平均粒子径）を評価した。
　表８～１０に、第１流体と第２流体の処理条件（処方及び運転条件）、第２流体の調製条件と得られた結果を示す。
　また、表８に示す第１流体及び第２流体の温度（目標温度）は、第１流体と第２流体のそれぞれを処理装置に導入する際の温調器（加熱・冷却）の設定温度であり、表９又は１０に示す第１流体と第２流体の温度は、第１流体と第２流体のそれぞれを処理装置に導入する直前（より詳しくは、処理用面１，２間に導入する直前）に、測定した温度である。 Next, the 20 wt% acetic acid / methanol (MeOH) is fed from the center as the first fluid precipitation solvent at a supply pressure / back pressure = 0.121 MPaG / 0.020 MPaG and a rotational speed of 2500 rpm, while the pigment solution is added to the first solution. Two fluids were introduced between the processing surfaces, and the first fluid and the second fluid were mixed in the thin film fluid. PR122 fine particle dispersion was discharged from between the processing surfaces 1 and 2. In order to remove impurities from the discharged PR122 fine particle dispersion, the PR122 fine particle dispersion was loosely agglomerated, and as a washing operation, the PR122 fine particle dispersion was precipitated by a centrifuge (× 18000G), and the supernatant was removed. Thereafter, pure water was added to re-disperse the PR122 fine particle dispersion, and the precipitate was precipitated again using a centrifuge. After performing the washing operation three times, the finally obtained PR122 fine particle dispersion paste was vacuum dried at 50 ° C. and −0.1 MPaG to obtain a dry powder of PR122 fine particles. The obtained dry powder of PR122 fine particles was subjected to TEM observation and XRD measurement, and the particle diameter, crystallinity, and β-type crystal ratio were determined. The values of the crystallinity and β-type crystal ratio are the ratios to the average particle diameter (hereinafter referred to as the crystallinity of PR122 fine particles / average particle diameter and the β-type crystals of PR122 fine particles as in Examples 1 to 22). (Ratio / average particle size).
Tables 8 to 10 show the processing conditions (formulation and operating conditions) for the first fluid and the second fluid, the preparation conditions for the second fluid, and the results obtained.
Further, the temperatures (target temperatures) of the first fluid and the second fluid shown in Table 8 are set temperatures of the temperature controller (heating / cooling) when each of the first fluid and the second fluid is introduced into the processing apparatus. Yes, the temperatures of the first fluid and the second fluid shown in Table 9 or 10 are just before introducing each of the first fluid and the second fluid into the processing apparatus (more specifically, introduced between the processing surfaces 1 and 2). The temperature measured immediately before).
Figure JPOXMLDOC01-appb-T000008
Figure JPOXMLDOC01-appb-T000008
Figure JPOXMLDOC01-appb-T000009
Figure JPOXMLDOC01-appb-T000009
Figure JPOXMLDOC01-appb-T000010
Figure JPOXMLDOC01-appb-T000010
　実施例２３～３１にて、第２流体の調製時間に対するＰＲ１２２微粒子の結晶化度／平均粒子径の変化を図１４に、実施例２３～３１にて、第２流体の調製時間に対するＰＲ１２２微粒子のβ型結晶比率／平均粒子径の変化を図１５に、実施例２３～３１にて、第２流体の調製温度に対するＰＲ１２２微粒子の結晶化度／平均粒子径の変化を図１６に、実施例２３～３１にて、第２流体の調製温度に対するＰＲ１２２微粒子のβ型結晶比率／平均粒子径の変化を図１７に示す。また、実施例３２～４０にて、第２流体の調製時間に対するＰＲ１２２微粒子の結晶化度／平均粒子径の変化を図１８に、実施例３２～４０にて、第２流体の調製時間に対するＰＲ１２２微粒子のβ型結晶比率／平均粒子径の変化を図１９に、実施例３２～４０にて、第２流体の調製温度に対するＰＲ１２２微粒子の結晶化度／平均粒子径の変化を図２０に、実施例３２～４０にて、第２流体の調製温度に対するＰＲ１２２微粒子のβ型結晶比率／平均粒子径の変化を図２１に示す。
　図１４～図１５、図１８～図１９より、第２流体の調製時間が増大すると、得られたＰＲ１２２微粒子の結晶化度／平均粒子径、β型結晶比率／平均粒子径の数値がともに増加する傾向が認められ、前記の調製時間の変化に加え第２流体の調製温度を変化させた実施例においても、同様の傾向が認められた。
　また、図１６～図１７、図２０～図２１より、第２流体の調製温度が増大すると、得られたＰＲ１２２微粒子の結晶化度／平均粒子径、β型結晶比率／平均粒子径の数値がともに変化することが認められた。前記の調製時間の変化に加え第２流体の調製温度を変化させた実施例においても、同様の傾向が認められた。
　また、表９～１０より、第２流体の調製時間が増大すると、得られたＰＲ１２２微粒子の平均粒子径が小さくなることが認められた。表９においては、第２流体の調製温度が増大すると、得られたＰＲ１２２微粒子の平均粒子径が小さくなる傾向が認められる。 In Examples 23 to 31, the change in crystallinity / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid is shown in FIG. 14, and in Examples 23 to 31, the change in PR122 fine particles with respect to the preparation time of the second fluid is shown in FIG. The change in β-type crystal ratio / average particle diameter is shown in FIG. 15 and in Examples 23 to 31, the change in crystallinity / average particle diameter of PR122 fine particles with respect to the preparation temperature of the second fluid is shown in FIG. FIG. 17 shows changes in β-type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation temperature of the second fluid at ˜31. In Examples 32 to 40, the change in crystallinity / average particle diameter of PR122 fine particles with respect to the preparation time of the second fluid is shown in FIG. 18, and in Examples 32 to 40, PR122 with respect to the preparation time of the second fluid. Changes in β-type crystal ratio / average particle size of fine particles are shown in FIG. 19, and changes in crystallinity / average particle size of PR122 fine particles with respect to the preparation temperature of the second fluid in Examples 32 to 40 are shown in FIG. In Examples 32 to 40, changes in β-type crystal ratio / average particle diameter of PR122 fine particles with respect to the preparation temperature of the second fluid are shown in FIG.
As shown in FIGS. 14 to 15 and FIGS. 18 to 19, as the preparation time of the second fluid increases, the values of crystallinity / average particle diameter and β-type crystal ratio / average particle diameter of the obtained PR122 fine particles both increase. The same tendency was recognized also in the Example which changed the preparation temperature of the 2nd fluid in addition to the change of the said preparation time.
Further, from FIGS. 16 to 17 and FIGS. 20 to 21, when the preparation temperature of the second fluid increases, the numerical values of crystallinity / average particle diameter, β-type crystal ratio / average particle diameter of the obtained PR122 fine particles are as follows. Both were found to change. The same tendency was observed in the examples in which the preparation temperature of the second fluid was changed in addition to the change in the preparation time.
Further, from Tables 9 to 10, it was confirmed that the average particle diameter of the obtained PR122 fine particles decreased as the preparation time of the second fluid increased. In Table 9, when the preparation temperature of 2nd fluid increases, the tendency for the average particle diameter of obtained PR122 microparticles | fine-particles to become small is recognized.
　本願の実施例においては、得られたＰＲ１２２微粒子について、β型結晶比率を求め、β型結晶比率／平均粒子径を評価したが、α型結晶である特定結晶型の構成比率（α型結晶比率）を求め、α型結晶比率／平均粒子径を評価してもよい。本願の実施例においては、攪拌エネルギーを規定する３つの条件（攪拌時間、攪拌翼の周速度、微粒子原料溶液の温度）のうち少なくとも１つを変化させて、攪拌エネルギーを増減させることにより変動するβ型結晶比率やα型結晶比率の変動率に比べ、平均粒子径の変動率が大きくなる傾向にあり、β型結晶比率／平均粒子径、α型結晶比率／平均粒子径の何れを評価しても同様の傾向を示すためである。 In the examples of the present application, the β-type crystal ratio was determined for the obtained PR122 fine particles, and the β-type crystal ratio / average particle diameter was evaluated. The composition ratio of the specific crystal type that is an α-type crystal (α-type crystal ratio) ) And the α-type crystal ratio / average particle diameter may be evaluated. In the embodiment of the present application, it fluctuates by changing at least one of the three conditions (stirring time, stirring blade peripheral speed, temperature of the fine particle raw material solution) that regulate the stirring energy, and increasing or decreasing the stirring energy. The variation rate of the average particle diameter tends to be larger than the variation rate of the β-type crystal ratio and α-type crystal ratio, and either β-type crystal ratio / average particle diameter or α-type crystal ratio / average particle diameter is evaluated. However, it is for showing the same tendency.
　本発明の製造方法の一例を示せば、粒子径、結晶化度及び結晶型が特定条件に設定された微粒子を製造するに際して、前記溶解ステップにおける前記攪拌翼の周速度条件を変化させることにより、前記析出ステップにおける前記微粒子の粒子径についての前記特定条件を充足する前記周速度条件を決定し、決定された前記周速度条件を維持しながら、前記攪拌時間条件と前記温度条件との少なくとも何れか一方を変化させることにより、前記析出ステップにおける前記微粒子の結晶化度及び結晶型についての前記特定条件を充足する前記攪拌時間条件と前記温度条件を決定することによって、粒子径、結晶化度及び結晶型が前記特定条件を充足する微粒子を製造するものとして実施することができる。
　本願の実施例１７～２２において、第２流体である顔料溶液調製時の攪拌翼の周速度を変化させることにより、得られたＰＲ１２２微粒子の平均粒子径についての特定条件を充足する周速度条件を決定する。ここで、特定条件をＰＲ１２２微粒子の平均粒子径の最も大きい実施例１７とし、その周速度である１８．８５ｍ／ｓｅｃを周速度条件として決定する。
　次に、本願の実施例４～１１において、前記周速度条件を維持しながら、第２流体の調製時間（攪拌時間）と調製温度との少なくとも何れか一方を変化させることにより、ＰＲ１２２微粒子の結晶化度及び結晶型についての特定条件を充足する攪拌時間条件と温度条件を決定する。ここで、「結晶化度」が高く、かつ「β型結晶比率」が高い実施例４（実施例１７）を特定条件とし、その調製時間（攪拌時間）である３０分を攪拌時間条件として決定する。
　さらに、本願の実施例１～３、４（実施例１７）において、「結晶化度」が高く、かつ「β型結晶比率」が高い実施例４（実施例１７）を特定条件とし、その温度（調製温度）である２８℃を温度条件として決定する。
　そして、粒子径、結晶化度及び結晶型が前記特定条件を充足する微粒子を製造するものとして実施することができる。
　前記の特定条件の設定はあくまで一例であっては、前記の一例に限定されるものではない。 If an example of the production method of the present invention is shown, when producing fine particles in which the particle diameter, crystallinity, and crystal type are set to specific conditions, by changing the peripheral speed condition of the stirring blade in the dissolution step, The peripheral speed condition that satisfies the specific condition for the particle diameter of the fine particles in the precipitation step is determined, and at least one of the stirring time condition and the temperature condition is maintained while the determined peripheral speed condition is maintained. By changing one of them, by determining the stirring time condition and the temperature condition satisfying the specific conditions for the crystallinity and crystal type of the fine particles in the precipitation step, the particle diameter, crystallinity and crystal It can be carried out as a mold for producing fine particles satisfying the specific conditions.
In Examples 17 to 22 of the present application, by changing the peripheral speed of the stirring blade at the time of preparing the pigment solution as the second fluid, the peripheral speed condition satisfying the specific condition for the average particle diameter of the obtained PR122 fine particles is decide. Here, the specific condition is Example 17 in which the average particle diameter of PR122 fine particles is the largest, and the peripheral speed of 18.85 m / sec is determined as the peripheral speed condition.
Next, in Examples 4 to 11 of the present application, by maintaining at least one of the second fluid preparation time (stirring time) and the preparation temperature while maintaining the peripheral speed condition, the PR122 fine particle crystals A stirring time condition and a temperature condition satisfying specific conditions for the degree of conversion and the crystal form are determined. Here, Example 4 (Example 17) having a high “crystallinity” and a high “β-type crystal ratio” was determined as a specific condition, and its preparation time (stirring time) of 30 minutes was determined as a stirring time condition. To do.
Further, in Examples 1 to 3 and 4 (Example 17) of the present application, Example 4 (Example 17) having a high “crystallinity” and a high “β-type crystal ratio” is set as a specific condition, and the temperature is set. 28 ° C. (preparation temperature) is determined as a temperature condition.
And it can implement as what manufactures the microparticles | fine-particles which a particle diameter, a crystallinity degree, and a crystal type satisfy the said specific conditions.
The setting of the specific condition is merely an example, and is not limited to the above example.
（貧溶媒法を用いたインドメタシン微粒子の作製）（実施例４１～４９）
　図１に示される流体処理装置を用いて、微粒子原料溶液であるインドメタシン溶液と析出溶媒とを、対向して配設された、接近・離反可能な処理用面をもつ、少なくとも一方が他方に対して回転する処理用面１，２間に形成される薄膜流体中で混合し、薄膜流体中でインドメタシン微粒子を析出させた。インドメタシン溶液の調製には、回転する攪拌翼を有する攪拌機を用いて行い、攪拌エネルギーを規定する３つの条件（攪拌時間、攪拌翼の周速度、微粒子原料溶液の温度）のうちインドメタシン溶液の温度（調製温度）及び／又は攪拌時間（調製時間）を変化させることにより、攪拌エネルギーを増減させた。 (Preparation of indomethacin fine particles using the poor solvent method) (Examples 41 to 49)
Using the fluid processing apparatus shown in FIG. 1, an indomethacin solution, which is a fine particle raw material solution, and a precipitation solvent are disposed so as to face each other and have an approachable / separable treatment surface, at least one of which is opposite to the other Were mixed in a thin film fluid formed between the rotating processing surfaces 1 and 2 to precipitate indomethacin fine particles in the thin film fluid. The indomethacin solution is prepared using a stirrer having a rotating stirring blade, and the temperature of the indomethacin solution (the stirring time, the peripheral speed of the stirring blade, and the temperature of the fine particle raw material solution) among the three conditions that regulate the stirring energy ( The stirring energy was increased or decreased by changing the preparation temperature) and / or the stirring time (preparation time).
　まず、図４及び図５に示す、回転する攪拌翼を有する攪拌機（クレアミックス（エム・テクニック株式会社製））を用いて、インドメタシン溶液を調製した。具体的には、クレアミックスを用いて、ジエチルエーテルを表１２の攪拌翼の周速度で攪拌しながらインドメタシンを投入し、表１２の調製時間、調製温度にてインドメタシン溶液を攪拌し、１．５ｗｔ％インドメタシン溶液を調製した。 First, an indomethacin solution was prepared using a stirrer (CLEAMIX (manufactured by M Technique Co., Ltd.)) having a rotating stirring blade shown in FIGS. Specifically, using Claremix, indomethacin was added while stirring diethyl ether at the peripheral speed of the stirring blade of Table 12, and the indomethacin solution was stirred at the preparation time and preparation temperature shown in Table 12, and 1.5 wt. A% indomethacin solution was prepared.
　次に、中央から第１流体の析出溶媒として、ヘキサンを、供給圧力／背圧力＝０．０８９ＭＰａＧ／０．０２０ＭＰａＧ、回転数１７００ｒｐｍで送液しながら、インドメタシン溶液を第２流体として処理用面間に導入し、第１流体と第２流体とを薄膜流体中で混合した。インドメタシン微粒子分散液が処理用面１，２間より吐出された。吐出されたインドメタシン微粒子分散液中より不純物を除去するために、インドメタシン微粒子分散液を緩く凝集させ、洗浄操作として遠心分離機（×８０００Ｇ）にてインドメタシン微粒子分散液を沈降させ、上澄み液を除去した後、純水を加えてインドメタシン微粒子分散液を再分散し、再度遠心分離機を用いて沈降させた。前記洗浄操作を３回行ったあと、最終的に得られたインドメタシン微粒子分散液のペーストを２５℃、－０．１ＭＰａＧにて真空乾燥し、インドメタシン微粒子の乾燥粉体を得た。得られたインドメタシン微粒子の乾燥粉体についてＴＥＭ観察とＸＲＤ測定を行い、粒子径、結晶化度並びにγ型結晶比率を求めた。また、結晶化度並びにγ型結晶比率のそれぞれの値については、実施例１～４０と同様、平均粒子径に対する割合（以下、インドメタシン微粒子の結晶化度／平均粒子径並びにインドメタシン微粒子のγ型結晶比率／平均粒子径）を評価した。
　表１１～１２に、第１流体と第２流体の処理条件（処方及び運転条件）、第２流体の調製条件と得られた結果を示す。
　また、表１１に示す第１流体及び第２流体の温度（目標温度）は、第１流体と第２流体のそれぞれを処理装置に導入する際の温調器（加熱・冷却）の設定温度であり、表１２に示す第１流体と第２流体の温度は、第１流体と第２流体のそれぞれを処理装置に導入する直前（より詳しくは、処理用面１，２間に導入する直前）に、測定した温度である。 Next, while feeding hexane from the center as the first fluid precipitation solvent at a supply pressure / back pressure of 0.089 MPaG / 0.020 MPaG and a rotation speed of 1700 rpm, the indomethacin solution is used as the second fluid between the processing surfaces. The first fluid and the second fluid were mixed in the thin film fluid. The indomethacin fine particle dispersion was discharged from between the processing surfaces 1 and 2. In order to remove impurities from the discharged indomethacin fine particle dispersion, the indomethacin fine particle dispersion was loosely aggregated, and the indomethacin fine particle dispersion was settled with a centrifuge (× 8000 G) as a washing operation, and the supernatant was removed. Thereafter, pure water was added to re-disperse the indomethacin fine particle dispersion, and the precipitate was precipitated again using a centrifuge. After performing the washing operation three times, the finally obtained paste of indomethacin fine particle dispersion was vacuum-dried at 25 ° C. and −0.1 MPaG to obtain a dry powder of indomethacin fine particles. The obtained dried powder of indomethacin fine particles was subjected to TEM observation and XRD measurement, and the particle diameter, crystallinity, and γ-type crystal ratio were determined. The values of crystallinity and γ-type crystal ratio are the ratios to the average particle size (hereinafter referred to as crystallinity / average particle size of indomethacin fine particles and γ-type crystals of indomethacin fine particles as in Examples 1 to 40). (Ratio / average particle size).
Tables 11 to 12 show the processing conditions (prescription and operating conditions) of the first fluid and the second fluid, the preparation conditions of the second fluid, and the obtained results.
Further, the temperatures (target temperatures) of the first fluid and the second fluid shown in Table 11 are set temperatures of the temperature controller (heating / cooling) when each of the first fluid and the second fluid is introduced into the processing apparatus. Yes, the temperatures of the first fluid and the second fluid shown in Table 12 are just before introducing each of the first fluid and the second fluid into the processing apparatus (more specifically, immediately before introducing between the processing surfaces 1 and 2). The measured temperature.
Figure JPOXMLDOC01-appb-T000011
Figure JPOXMLDOC01-appb-T000011
Figure JPOXMLDOC01-appb-T000012
Figure JPOXMLDOC01-appb-T000012
　実施例４１～４９にて、第２流体の調製時間に対するインドメタシン微粒子の結晶化度／平均粒子径の変化を図２２に、実施例４１～４９にて、第２流体の調製温度に対するインドメタシン微粒子の結晶化度／平均粒子径の変化を図２３に示す。また、実施例４１～４９にて、第２流体の調製時間に対するインドメタシン微粒子のγ型結晶比率／平均粒子径の変化を図２４に、実施例４１～４９にて、第２流体の調製温度に対するインドメタシン微粒子のγ型結晶比率／平均粒子径の変化を図２５に示す。 In Examples 41 to 49, the change in crystallinity / average particle diameter of indomethacin fine particles with respect to the preparation time of the second fluid is shown in FIG. The change in crystallinity / average particle diameter is shown in FIG. Further, in Examples 41 to 49, the change in γ-type crystal ratio / average particle size of indomethacin fine particles with respect to the preparation time of the second fluid is shown in FIG. FIG. 25 shows the change in γ-type crystal ratio / average particle diameter of indomethacin fine particles.
　第２流体の調製条件に関して同一の調製温度（実施例４１～４３、実施例４４～４６及び実施例４７～４９）で比較すると、調製温度が３３℃、２５℃、５℃の何れの場合においても、調製時間が増加するにつれて得られるインドメタシン微粒子の平均粒子径が減少し、結晶化度／平均粒子径とγ型結晶比率／平均粒子径がともに増加する傾向が表れている。
　また、第２流体の調製条件に関して同一の調製時間（実施例４１、４４、４７、実施例４２、４５、４８及び実施例４３、４６、４９）で比較すると、調製時間が１５分、３０分、６０分の何れの場合においても、調製温度が上昇するにつれて得られるインドメタシン微粒子の平均粒子径が増加し、結晶化度／平均粒子径とγ型結晶比率／平均粒子径がともに減少する傾向が表れている。
　図２２及び図２４を参照すると、第２流体の調製時間が短い間（調製時間を１５分とした場合）は、第２流体の調製温度の高低に拘わらず、得られるインドメタシン微粒子の結晶化度／平均粒子径及びγ型結晶比率／平均粒子径に関して差が殆ど発生しなくなることがわかる。第２流体の調製時間を６０分とした場合は、調製温度の高低に応じて、得られるインドメタシン微粒子の結晶化度／平均粒子径及びγ型結晶比率／平均粒子径の差が非常に大きい。第２流体の調製時間を３０分とした場合は、調製温度の高低に応じて、得られるインドメタシン微粒子の結晶化度／平均粒子径及びγ型結晶比率／平均粒子径の差が発生するものの、第２流体の調製時間が６０分の場合に比べると差は減少している。つまり、図２２及び図２４を参照すると、第２流体の調製時間に対するインドメタシン微粒子の結晶化度／平均粒子径の変化量及びγ型結晶比率／平均粒子径の変化量は、第２流体の調製温度が高いほど小さくなる。この場合の制御方法の一例を示せば、まずは第２流体の調製温度を高く設定した後、第２流体の調製時間を設定することによって、所望の結晶化度／平均粒子径の変化及びγ型結晶比率／平均粒子径を容易に得ることができる。また、第２流体の調製時間が同一で結晶化度／平均粒子径、γ型結晶比率／平均粒子径を大きくするには調製温度を低く設定すればよく、第２流体の調製時間が同一で結晶化度／平均粒子径、γ型結晶比率／平均粒子径を小さくするには調製温度を高く設定すればよい。
　図２３及び図２５を参照すると、第２流体の調製温度を室温よりも若干高めの３３℃に保つことによって、第２流体の調製時間の長短に拘わらず、得られるインドメタシン微粒子の結晶化度／平均粒子径及びγ型結晶比率／平均粒子径に関して差が殆ど発生しなくなることがわかる。第２流体の調製温度が５℃の場合は、調製時間の長短に応じて、得られるインドメタシン微粒子の結晶化度／平均粒子径及びγ型結晶比率／平均粒子径の差が非常に大きい。第２流体の調製温度を室温近傍の２５℃に保った場合は、調製時間の長短に応じて、得られるインドメタシン微粒子の結晶化度／平均粒子径及びγ型結晶比率／平均粒子径の差が発生するものの、第２流体の調製温度が５℃の場合に比べると差は減少している。つまり、図２３及び図２５を参照すると、第２流体の調製温度に対するインドメタシン微粒子の結晶化度／平均粒子径の変化量及びγ型結晶比率／平均粒子径の変化量は、第２流体の調製時間が短いほど小さくなる。この場合の制御方法の一例を示せば、まずは第２流体の調製時間を短時間に設定した後、第２流体の調製温度を設定することによって、所望の結晶化度／平均粒子径の変化及びγ型結晶比率／平均粒子径を容易に得ることができる。また、第２流体の調製温度が同一で結晶化度／平均粒子径、γ型結晶比率／平均粒子径を大きくするには調製時間を長く設定すればよく、第２流体の調製温度が同一で結晶化度／平均粒子径、γ型結晶比率／平均粒子径を小さくするには調製時間を短く設定すればよい。 When the preparation conditions of the second fluid were compared at the same preparation temperature (Examples 41 to 43, Examples 44 to 46, and Examples 47 to 49), the preparation temperature was 33 ° C., 25 ° C., or 5 ° C. However, as the preparation time increases, the average particle size of the indomethacin fine particles obtained decreases, and both the crystallinity / average particle size and the γ-type crystal ratio / average particle size tend to increase.
Further, when the same preparation time (Examples 41, 44, 47, Examples 42, 45, 48 and Examples 43, 46, 49) was compared with respect to the preparation conditions of the second fluid, the preparation time was 15 minutes, 30 minutes. In any case of 60 minutes, the average particle diameter of the indomethacin fine particles obtained increases as the preparation temperature rises, and both the crystallinity / average particle diameter and the γ-type crystal ratio / average particle diameter tend to decrease. Appears.
Referring to FIGS. 22 and 24, while the preparation time of the second fluid is short (when the preparation time is 15 minutes), the crystallinity of the indomethacin microparticles obtained regardless of the preparation temperature of the second fluid. It can be seen that there is almost no difference between / average particle size and γ-type crystal ratio / average particle size. When the preparation time of the second fluid is 60 minutes, the difference in crystallinity / average particle diameter and γ-type crystal ratio / average particle diameter of the indomethacin fine particles obtained is very large depending on the preparation temperature. When the preparation time of the second fluid is 30 minutes, although the difference in crystallinity / average particle diameter and γ-type crystal ratio / average particle diameter of the indomethacin fine particles obtained depends on the preparation temperature, The difference is reduced compared to the case where the preparation time of the second fluid is 60 minutes. That is, referring to FIG. 22 and FIG. 24, the degree of crystallinity of the indomethacin fine particles / average particle size change and the amount of change in the γ-type crystal ratio / average particle size with respect to the preparation time of the second fluid are as follows. The higher the temperature, the smaller. An example of the control method in this case is as follows. First, the preparation temperature of the second fluid is set high, and then the preparation time of the second fluid is set to thereby change the desired crystallinity / average particle diameter and γ type. The crystal ratio / average particle diameter can be easily obtained. Further, in order to increase the crystallinity / average particle diameter and γ-type crystal ratio / average particle diameter with the same preparation time of the second fluid, the preparation temperature may be set low, and the preparation time of the second fluid is the same. In order to reduce the crystallinity / average particle diameter and the γ-type crystal ratio / average particle diameter, the preparation temperature may be set high.
Referring to FIGS. 23 and 25, by maintaining the preparation temperature of the second fluid at 33 ° C., which is slightly higher than room temperature, the crystallinity / degree of the indomethacin fine particles obtained can be obtained regardless of the preparation time of the second fluid. It can be seen that there is almost no difference between the average particle diameter and the γ-type crystal ratio / average particle diameter. When the preparation temperature of the second fluid is 5 ° C., the difference in crystallinity / average particle diameter and γ-type crystal ratio / average particle diameter of the indomethacin fine particles obtained is very large depending on the length of the preparation time. When the preparation temperature of the second fluid is kept at 25 ° C. near room temperature, the difference in crystallinity / average particle diameter and γ-type crystal ratio / average particle diameter of the indomethacin fine particles obtained depends on the length of the preparation time. Although it occurs, the difference is reduced compared to the case where the preparation temperature of the second fluid is 5 ° C. That is, referring to FIGS. 23 and 25, the degree of crystallinity / average particle size change and the amount of change in γ-type crystal ratio / average particle size of indomethacin microparticles with respect to the preparation temperature of the second fluid are as follows. The shorter the time, the smaller. An example of the control method in this case is as follows. First, the preparation time of the second fluid is set to a short time, and then the preparation temperature of the second fluid is set to thereby change the desired crystallinity / average particle diameter and The γ-type crystal ratio / average particle diameter can be easily obtained. Further, in order to increase the crystallinity / average particle diameter and the γ-type crystal ratio / average particle diameter when the preparation temperature of the second fluid is the same, the preparation time of the second fluid should be set long. In order to reduce the crystallinity / average particle diameter and γ-type crystal ratio / average particle diameter, the preparation time may be set short.
　　１　　　第１処理用面
　　２　　　第２処理用面
　　１０　　第１処理用部
　　１１　　第１ホルダ
　　２０　　第２処理用部
　　２１　　第２ホルダ
　　ｄ１　　第１導入部
　　ｄ２　　第２導入部
　　ｄ２０　開口部 DESCRIPTION OF SYMBOLS 1 1st processing surface 2 2nd processing surface 10 1st processing part 11 1st holder 20 2nd processing part 21 2nd holder d1 1st introduction part d2 2nd introduction part d20 Opening part

Claims (8)

  1. 回転する攪拌翼を有する攪拌機を用いて、少なくとも１種類の微粒子原料を溶媒に溶解させて微粒子原料溶液を得る溶解ステップと、
    前記微粒子原料溶液から前記微粒子原料を析出させるための少なくとも１種類の析出溶媒と、前記微粒子原料溶液とを、対向して配設された、接近・離反可能な、少なくとも一方が他方に対して相対的に回転する少なくとも２つの処理用面間に導入し、前記少なくとも２つの処理用面間に形成される薄膜流体中で混合して、微粒子を析出させる析出ステップとを備えた微粒子の製造方法において、
    前記溶解ステップにて、前記攪拌機による攪拌時間条件、前記攪拌翼の周速度条件、前記微粒子原料溶液の温度条件とにて規定される攪拌エネルギーを、前記条件のうち少なくとも１つを変化させることにより、増減させ、
    前記攪拌エネルギーの増減によって、前記析出ステップで得られる前記微粒子の結晶化度を制御することを特徴とする微粒子の製造方法。     Using a stirrer having a rotating stirring blade, a dissolving step of dissolving at least one kind of fine particle raw material in a solvent to obtain a fine particle raw material solution;
    At least one kind of precipitation solvent for precipitating the fine particle raw material from the fine particle raw material solution and the fine particle raw material solution are arranged to face each other, and at least one is relative to the other. And a precipitation step of precipitating the fine particles by introducing them between the at least two processing surfaces that are rotated and mixing in a thin film fluid formed between the at least two processing surfaces. ,
    In the dissolving step, by changing at least one of the above conditions, the stirring energy defined by the stirring time condition by the stirrer, the peripheral speed condition of the stirring blade, and the temperature condition of the fine particle raw material solution is changed. , Increase or decrease
    A method for producing fine particles, wherein the crystallinity of the fine particles obtained in the precipitation step is controlled by increasing or decreasing the stirring energy.
  2. 回転する攪拌翼を有する攪拌機を用いて、少なくとも１種類の微粒子原料を溶媒に溶解させて微粒子原料溶液を得る溶解ステップと、
    前記微粒子原料溶液から前記微粒子原料を析出させるための少なくとも１種類の析出溶媒と、前記微粒子原料溶液とを、対向して配設された、接近・離反可能な、少なくとも一方が他方に対して相対的に回転する少なくとも２つの処理用面間に導入し、前記少なくとも２つの処理用面間に形成される薄膜流体中で混合して、微粒子を析出させる析出ステップとを備えた微粒子の製造方法において、
    前記溶解ステップにて、前記攪拌機による攪拌時間条件、前記攪拌翼の周速度条件、前記微粒子原料溶液の温度条件とにて規定される攪拌エネルギーを、前記条件のうち少なくとも１つを変化させることにより、増減させ、
    前記攪拌エネルギーの増減によって、前記析出ステップで得られる前記微粒子の結晶型を制御することを特徴とする微粒子の製造方法。     Using a stirrer having a rotating stirring blade, a dissolving step of dissolving at least one kind of fine particle raw material in a solvent to obtain a fine particle raw material solution;
    At least one kind of precipitation solvent for precipitating the fine particle raw material from the fine particle raw material solution and the fine particle raw material solution are arranged to face each other, and at least one is relative to the other. And a precipitation step of precipitating the fine particles by introducing them between the at least two processing surfaces that are rotated and mixing in a thin film fluid formed between the at least two processing surfaces. ,
    In the dissolving step, by changing at least one of the above conditions, the stirring energy defined by the stirring time condition by the stirrer, the peripheral speed condition of the stirring blade, and the temperature condition of the fine particle raw material solution is changed. , Increase or decrease
    A method for producing fine particles, wherein the crystal form of the fine particles obtained in the precipitation step is controlled by increasing or decreasing the stirring energy.
  3. 前記溶解ステップにおける前記攪拌エネルギーを増加させることにより、前記微粒子の粒子径に対する前記微粒子の結晶化度の比率が上昇するように制御することを特徴とする請求項１記載の微粒子の製造方法。 2. The method for producing fine particles according to claim 1, wherein the ratio of the crystallinity of the fine particles to the particle diameter of the fine particles is controlled to increase by increasing the stirring energy in the dissolving step.
  4. 前記微粒子は複数の結晶型を有し、複数の結晶型の結晶成分に対する特定の結晶型の結晶成分の比率を特定結晶型の構成比率とするものであり、
    前記溶解ステップにおける前記攪拌エネルギーを増加させることにより、前記微粒子の粒子径に対する前記特定結晶型の構成比率の比率が上昇するように制御することを特徴とする請求項２記載の微粒子の製造方法。     The fine particles have a plurality of crystal types, and a ratio of a crystal component of a specific crystal type to a crystal component of a plurality of crystal types is a constituent ratio of the specific crystal type,
    3. The method for producing fine particles according to claim 2, wherein the ratio of the composition ratio of the specific crystal type to the particle diameter of the fine particles is controlled to increase by increasing the stirring energy in the dissolving step.
  5. 前記微粒子が、顔料微粒子であることを特徴とする請求項１～４の何れかに記載の微粒子の製造方法。 The method for producing fine particles according to any one of claims 1 to 4, wherein the fine particles are pigment fine particles.
  6. 前記析出ステップは、アシッドペースティング法、アルカリペースト法、又は貧溶媒法によって前記微粒子を析出するものであることを特徴とする請求項３又は４に記載の微粒子の製造方法。 5. The method for producing fine particles according to claim 3, wherein the precipitation step is to deposit the fine particles by an acid pasting method, an alkali paste method, or a poor solvent method.
  7. 前記微粒子が、顔料微粒子であることを特徴とする請求項６に記載の微粒子の製造方法。 The method for producing fine particles according to claim 6, wherein the fine particles are pigment fine particles.
  8. 回転する攪拌翼を有する攪拌機を用いて、少なくとも１種類の微粒子原料を溶媒に溶解させて微粒子原料溶液を得る溶解ステップと、
    前記微粒子原料溶液から前記微粒子原料を析出させるための少なくとも１種類の析出溶媒と、前記微粒子原料溶液とを、対向して配設された、接近・離反可能な、少なくとも一方が他方に対して相対的に回転する少なくとも２つの処理用面間に導入し、前記少なくとも２つの処理用面間に形成される薄膜流体中で混合して、微粒子を析出させる析出ステップとを備えた微粒子の製造方法において、
    前記溶解ステップにて、前記攪拌機による攪拌時間条件、前記攪拌翼の周速度条件、前記微粒子原料溶液の温度条件とにて規定される攪拌エネルギーを、前記条件のうち少なくとも１つを変化させることにより、増減させ、
    粒子径、結晶化度及び結晶型が特定条件に設定された微粒子を製造するに際して、
    前記溶解ステップにおける前記周速度条件と前記攪拌時間条件と前記温度条件とのうち１つの条件（第１条件）を変化させ、他の２つの条件（第２第３条件）を固定することにより、前記析出ステップにおける前記微粒子の粒子径、結晶化度及び結晶型のうちの少なくとも１つについて前記特定条件を充足する前記第１条件を決定し、
    決定された前記第１条件を維持しながら、前記第２第３条件のうち少なくとも何れか一方を変化させることにより、前記析出ステップにおける前記微粒子の粒子径、結晶化度及び結晶型のうちの前記少なくとも１つとは異なる残りの２つについての前記特定条件を充足する前記周速度条件と前記攪拌時間条件と前記温度条件のうちの前記第１条件とは異なる前記第２第３条件を決定することによって、粒子径、結晶化度及び結晶型が前記特定条件を充足する微粒子を製造することを特徴とする微粒子の製造方法。     Using a stirrer having a rotating stirring blade, a dissolving step of dissolving at least one kind of fine particle raw material in a solvent to obtain a fine particle raw material solution;
    At least one kind of precipitation solvent for precipitating the fine particle raw material from the fine particle raw material solution and the fine particle raw material solution are arranged to face each other, and at least one is relative to the other. And a precipitation step of precipitating the fine particles by introducing them between the at least two processing surfaces that are rotated and mixing in a thin film fluid formed between the at least two processing surfaces. ,
    In the dissolving step, by changing at least one of the above conditions, the stirring energy defined by the stirring time condition by the stirrer, the peripheral speed condition of the stirring blade, and the temperature condition of the fine particle raw material solution is changed. , Increase or decrease
    When producing fine particles in which the particle diameter, crystallinity and crystal type are set to specific conditions,
    By changing one condition (first condition) among the peripheral speed condition, the stirring time condition and the temperature condition in the melting step, and fixing the other two conditions (second third condition), Determining the first condition that satisfies the specific condition for at least one of the particle size, crystallinity, and crystal type of the fine particles in the precipitation step;
    By changing at least one of the second and third conditions while maintaining the determined first condition, the particle size, crystallinity, and crystal type of the fine particles in the precipitation step are changed. Determining the second and third conditions different from the first condition among the peripheral speed condition, the stirring time condition, and the temperature condition satisfying the specific condition for the remaining two different from at least one To produce fine particles having a particle diameter, a crystallinity, and a crystal type satisfying the specific conditions.
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